Case Report, Int J Ophthalmic Pathol Vol: 0 Issue: 0
Whiplash-Associated Accommodative Spasm Treated with Gamma-Amino-Butyric Acid Agonist
*Corresponding Author : Aurelio Imburgia
Department of Ophthalmology, Ospedale di Stato della Repubblica di San Marino, San Marino, via bagaro 12, Ferrara, Italy
Received: June 13, 2017 Accepted: July 07, 2017 Published: July 14, 2017
Citation: Imburgia A, Sorrentino FS, Mularoni A (2017) Whiplash-Associated Accommodative Spasm Treated with Gamma-Amino-Butyric Acid Agonist. Int J Ophthalmic Pathol 6:3. doi: 10.4172/2324-8599.1000205
Spasm of the near reflex is characterized by miosis, excessive convergence and accommodative spasm (pseuomyopia) that usually occurs, on a functional basis, in young adults with underlying psychiatric disorders (anxiety, depression, hysteria). When this disorders occurs on a functional basis, miosis is always present as well as variable degrees of convergence and accommodation with pseudomyopia. Accommodative spasm can also occur after a head injury as isolated entity of spasm of the near reflex and causes symptoms (blurred vision, headache, and nausea) that are reversible after cycloplegia. Spasm usually resolves spontaneously after 1-2 years from the head injury, but in some cases may persist for a long time and cycloplegics not provide an effective and definitive solution to the problem. We report a patient with a whiplash-associated accommodative spasm and pseudomyopia, treated with GABA-B receptor agonist (Baclofen) that improved accommodative spasm.
Keywords: Spasm; Blurred vision; Pseudomyopia
Spasm of the near reflex is characterized by meiosis, excessive convergence and accommodative spasm (pseuomyopia) that usually occurs, on a functional basis, in young adults with underlying psychiatric disorders (anxiety, depression, hysteria) . When this disorder occurs on a functional basis, meiosis is always present as well as variable degrees of convergence and accommodation with pseudomyopia . Accommodative spasm can also occur after a head injury as isolated entity of spasm of the near reflex  and causes symptoms (blurred vision, headache, and nausea) that are reversible after cycloplegia. Spasm usually resolves spontaneously after 1-2 years from the head injury, but in some cases may persist for a long time and cycloplegics not provide an effective and definitive solution to the problem [2,3]. We report a patient with a whiplash-associated accommodative spasm and pseudomyopia, treated with GABA-B receptor agonist (Baclofen) that improved accommodative spasm.
In April 2016, a 34 year old man was examined for blurred vision and headache. Medical history reported a few days before the car accident with whiplash. Slit-lamp examination of both eyes was normal (including biomicroscopy and applanation tonometry), pupils were isochoric, isocyclic and reactive to light, direct and consensual pupillary light reflexes were regular and were not found alterations in ocular motility and convergence. Autorefractometry showed high myopia in both eyes and best-corrected visual acuity was OD 20/200 (-12.00 sph -3.00 cyl × 30) and OS 20/200 (-12.00 sph -3.00 cyl × 165 TABO). After cycloplegia with 1% cyclopentolate, best-corrected visual acuity improved to 20/25 in both eyes with a considerable reduction of myopia (OD -2.75 sph -1.50 cyl × 30 and OS -2.75 sph -1.50 cyl × 165 TABO). Fundus examination showed crowded optic discs and no alterations in macular profile. Macular and RNFL OCT were normal as well as diagnostic imaging (CT, NMR, VEP, MEP, Echo color Doppler of carotid vessels); A-scan ultrasound biometry showed a slight axial myopia. Neurological examination highlighted neck stiffness, nausea and peripheral vertigo with post-traumatic neck pain and headache due to whiplash. Diagnosis of accommodative spasm with pseudomyopia and photo-accommodative dissociation of pupillary reflexes was made. The patient was initially treated with atropine 1% once a day, but whenever he suspended therapy accommodative spasm resurfaced. To resolve the neck stiffness, a consultation with a neurologist was made and the patient was initially treated with benzodiazepine (GABA-A receptor agonist). After a week without improvements, the therapy was modified by replacing benzodiazepine with Baclofen (GABA-B receptor agonist). The patient returned after a month of therapy and autorefractometry surprisingly showed an improvement of accommodative spasm (OD -2.75 sphere, -1.50 cylinder ax 30 and OS -2.75 sphere -1.50 cylinder ax 165 TABO) as well as neurological symptoms. He reported that blurred vision stopped after 10 days of treatment with Baclofen. Initially, he manifested drowsiness and fatigue, but these symptoms subsided after the first week of treatment. For the first month the treatment was administered at full dose, i.e., 25 mg of Baclofen for three times a day; then the administration was gradually interrupted, but the spasm reappeared. Finally the correct dose was found and currently the patient takes baclofen 25 mg one time per day with an improvement of spasm and without side effects (Table 1).
|Atropine 1% (Follow-up 1: One week from baseline)||Cessation of treatment with cyclopentolate 1% (Follow-up 2: Two weeks from baseline)||Baclofen (Follow-up 3: One month from baseline)||Gradually cessation of Baclofen (Follow-up 4: Two months from baseline)||Minimum dose of Baclofen (Follow-up 5: Four months from baseline)|
|Visual acuity||OD: 20/200||OD: 20/25||OD: 20/200||OD: 20/25||OD: 20/200||OD: 20/25|
|OS: 20/200||OS: 20/25||OS: 20/200||OS: 20/25||OS: 20/200||OS: 20/25|
|Refraction||OD: -12.00 D||OD: -2.75 D||OD: -12.00 D||OD: -2.75 D||OD: -12.00 D||OD: -2.75 D|
|OS: -12.00 D||OS: -2.75 D||OS: -12.00 D||OS: -2.75 D||OS: -12.00 D||OS: -2.75 D|
|Refraction||OD: -12.00 D||OD: -2.75 D||OD: -12.00 D||OD: -2.75 D||OD: -12.00 D||OD: -2.75 D|
|OS: -12.00 D||OS: -2.75 D||OS: -12.00 D||OS: -2.75 D||OS: -12.00 D||OS: -2.75 D|
|Pupillar reflexes Neurological symptoms (neck stiffness, whiplash)||Present||Present||Present||Absent||Present||Absent|
Table 1: Summary of clinical findings.
The near response complex includes three elements: accommodation, convergence and pupillary constriction. Accommodation is a physiological reflex modifying the curvature and shape of the crystalline lens, so as to focus objects at different distances.
Neural pathway of the accommodative system is the following: retinal cones, stimulated by defocus blur, transmit blur signals through magnocellular layer of lateral geniculate nucleus to primary visual cortex. Cortical cells process supranuclear blur signals and transmit in the midbrain to Edinger-Westphal nucleus where motor command is formulated. Efferent pathway penetrates into the orbit following the oculomotor nerve (III C.N.) up to reach the ciliary ganglion, from which originate post-ganglionic fibers (short ciliary nerves) innervating the ciliary muscle (parasympathetic innervation). The contraction of the ciliary muscle causes a relaxation of zonular fibers resulting in change of the thickness and curvature of the crystalline lens to obtain an in-focus retinal image and clarity of vision .
The Edinger-Westphal nucleus also contains neurons controlling pupillary motility. Erichsen and May  investigated the distribution of preganglionic motoneurons supplying the ciliary ganglion in the cat, suggesting a rostral localization of the pupil-related preganglionic motoneurons (that is, those controlling the iris sphincter pupillae muscle) in EW nucleus, while lens-related preganglionic motoneurons controlling the ciliary muscle were particularly prevalent caudally in the EW nucleus. In addition, Jampel identified a discrete cell mass within the third nerve nucleus subserving accommodation and a discrete cell mass sub serving pupillary constriction . By faradic stimulation of the preoccipital cerebral cortex of the monkey, Jampal showed the separateness of the components of the near reflex . These findings may explain the photo-accommodative dissociation of our patient, assuming an alteration only at the level of the group of neurons controlling accommodation, resulting in separation of the photo-accommodative reflex.
Furthermore, Edinger-Westphal nucleus receives important supranuclear influences regulating accommodative reflex . The midbrain reticular formation of the dorsomedial division adjacent to the magnocellular red nucleus (MRFdmMRN) is the supranuclear organization which converges the sensory-motor cortical activities on the centers of the near-reflex triad and becomes an integration center for each nucleus in the oculomotor nuclear complex . The lateral suprasylvian (LS) area in the cat has been related to all three components of the ocular near response since microstimulation in this area evoked intra- and extra-ocular movements. The LS area could play an important role in triggering and modulating component movements in the ocular near response . It has been reported that electrical stimulation of the cerebellar nuclei (nucleus fastigius and nucleus interpositus bilaterally) evokes a discharge in the short ciliary nerves suggesting a direct excitatory connexion from cerebellar efferent to the preganglionic neurons in the Edinger- Westphal nucleus, controlling the accommodation system [11,12]. An alteration of cerebellar influences on oculomotor nuclei may result in the abnormal dynamic accommodation with the triggering of the accommodative spasm . Other lesions secondary to head trauma were found in patients with subsequent persistent accommodative spasm include those in frontal and parieto-occipital regions, periventricular locations, left temporal lobe and cerebellum .
Although accommodative insufficiency is the most common abnormality analyzed in head injury [15,16], several authors have reported spasm of accommodation after head trauma [2-4,17,18]. In all cases, they underlined that cycloplegics, plus lenses or minus lenses did not provide an effective and consistent solution to the problem. Although atropine produced an immediate improvement, it was not effective in the long term. Some authors underlined the usefulness of treatment with botulinum toxin (2.5 iu Botox®) in combination with a visual therapy program based on the stimulation of fusional divergence, diplopia and stereopsis consciousness in patients with spasm of the near reflex with predominant component of esotropia . In our case, the main component was accommodative spasm and we have not considered this possibility. Some authors have suggested the extraction of clear lens as treatment of persistent accommodative spasm after head trauma , but we have not considered this option due to the young age of our patient.
Chan and Trobe  have reported six cases of accommodative spasm without other components of the near reflex following severe brain injury in young adults. They have suggested that this phenomenon may represent a traumatic activation or disinhibition of putative supranuclear centers regulating accommodation, although at present the pathophysiological mechanism is uncertain. Ohashi et al.  reported a 57-year–old man with persistent convergence and miosis caused by head trauma that completely disappeared after intravenous injections of benzodiazepine, suggesting that the disturbance of the GABAergic inhibitory system in the near reflex may be responsible for the occurrence of the spasm.
In our case, Benzodiazepines (GABA-A receptor agonist) were administered initially, but not improved the spasm, while Baclofen, a drug similar to benzodiazepines, but with different receptor affinity (GABA-B receptor agonist), was effective in the resolution of accommodative spasm.
Since diagnostic imaging was normal and medical history reported a new cervical trauma and neurological symptoms, pathophysiological mechanism hypothesized was a post-traumatic dysfunction of putative inhibitory pathways that regulate the process of accommodation by sending GABAergic inhibitory signals in the Edinger-Westphal nucleus. Therefore accommodative spasm was due to an imbalance between excitatory and inhibitory pulses of accommodation. In this sense, Baclofen restored the affected GABAergic transmission.
Baclofen is normally used for spasticity management. It acts both pre- and post-synaptically to inhibit spinal reflexes through a stimulation of GABA-B receptors that inhibit the release of excitatory amino acids (glutamate and aspartate). Baclofen is rapidly and completely absorbed by enteral administration. The peak plasma concentration is reached after about 1-1.5 h after ingestion and it has a mean half-life of 3.5 h. It is metabolized by the liver and eliminated by renal excretion. Besides inhibiting spinal reflexes, Baclofen also acts on the cortex because readily crosses the blood-brain barrier. The most common adverse effects are fatigue, drowsiness, sedation, dizziness, cognitive dysfunction and lowering of the seizure threshold. The typical starting dose is 5-10 mg two or three times per day, and the dosage can be increased up to 80-100 mg per day. In cases of neck pain, Baclofen leads to a significant attenuation of symptoms (pain, stiffness, fatigue) because it breaks the vicious circle in which the muscular contraction, increasing the mechanical compression in the cervical spine, determines the maintenance of symptoms. A Baclofen withdrawal syndrome can occur with rapid cessation of usage. Withdrawal symptoms include a rebound increase in spasticity, fever, altered mental status, seizures, malignant hyperthermia, and, very rarely, death. Baclofen overdose syndrome can also occur. It is characterized by sedation, depressed arousal, and respiratory suppression and is treated by temporarily stopping or tapering off baclofen .
In our case, NMR failed to show abnormalities in the mid-brain. Although it is possible that he has small mesencephalic lesions, not detected by NMR, the findings in our case suggest a supranuclear origin for accommodative dysfunction. Even if a functional basis for the disorder should be always suspected in young adults, we can assume that the effectiveness of baclofen suggests disturbance of GABAergic inhibition in the near reflex as an organic mechanism, although at present the pathological mechanism is uncertain. We think that baclofen may be an effective drug option for treatment of refractory post-traumatic accommodative spasm. The few side effects and more specific receptor affinity (GABA-B receptor); make this drug ideal for the treatment of these cases.
The study was approved by the local Ethics Committee and written informed consent was given by the patient.
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