Ординатура / Офтальмология / Английские материалы / Advances in Understanding Mechanisms and Treatment of Infantile Forms of Nystagmus_Leigh, Devereaux_2008

ABSTRACT

Our objective was to describe a case of pseudoabducens palsy due to a midbrain lesion. The method employed was interpretation of clinical findings using both old and modern anatomical concepts. A 49-year-old patient presented with insidious onset of double vision on right lateral gaze. His examination demonstrated a minor abduction deficit of the right eye, which remained unchanged over an observation period of 2.5 years. After initially negative neuroimaging, a small lesion appeared at the ipsilateral, posterior mesencephalo-diencephalic junction on follow-up MRIs. An eye movement recording demonstrated findings indistinguishable from a mild sixth nerve palsy. There was no involvement of vertical gaze or pupillary motility. We found that isolated prenuclear abduction deficits can occur in conjunction with an ipsilateral midbrain lesion. Possible mechanisms of impaired abduction are discussed.

In 1923, Anton Lutz (1883–1948) published a detailed review of anatomical structures controlling eye movements in the cerebral hemispheres, the brainstem, and the cerebellum.1 Modern concepts of internuclear connections between the sixth and third nerve nuclei had not yet evolved, and Lutz proposed his own scheme for horizontal gaze control in the brainstem (Fig. 21.1). This consisted of a supranuclear crossed pathway that split into ascending and descending branches at the

level of the mid-pons. Lutz correlated internuclear ophthalmoplegia (INO) with a lesion of the ascending branch and applied the term anterior INO to this condition. In contrast, a lesion of the descending branch at the pontine level would cause a prenuclear palsy of abduction, which Lutz referred to as posterior INO. Lutz’s anatomical conjectures were eventually proved incorrect, but the possibility of prenuclear abduction weakness continues to be discussed in the literature. So far, however, no case of isolated, unilateral abduction weakness with radiological confirmation of a supranuclear lesion site has been identified. We describe a patient presenting with mild abduction weakness mimicking a peripheral sixth nerve palsy. His ocular motor deficit correlated with a small, upper-brainstem lesion.

CASE REPORT

This 49-year-old, otherwise healthy patient presented with a six-month history of mild horizontal image dissociation on rightward gaze of insidious onset. He reported no associated local or generalized symptoms. The ocular history was only significant for presbyopia and remote, mild orbital trauma that had resolved without sequelae. Initial neuroimaging and laboratory workup for myasthenia, thyroid disease, and systemic infectious and inflammatory disorders was negative. On first examination, the patient had a minor abduction deficit to the right (Fig. 21.2; also see color insert ) associated with a 5 prism diopter esophoria in primary gaze that increased to 18 prism diopters on rightward gaze.

Figure 21.1 Lutz’s schematic of supranuclear innervation of the contralateral third and sixth nerve nuclei. Note that the pathway splits into an ascending segment to the third nerve nucleus, which controls the opposite medial rectus muscle, and a descending portion to the abducens nucleus. “Posterior INO of Lutz” results from disruption of the descending pathway, while internuclear adduction weakness is caused by lesions involving the ascending portion. This schematic corresponds with Figure 4 in Lutz’s 1923 article. Source: Lutz A. Ueber die Bahnen der Blickwendung und deren Dissoziierung (nebst Mitteilung eines Falles von Ophthalmoplegia internuclearis anterior in Verbindung mit Dissoziierung der Bogengänge) [On ocular motor pathways and dissociated ocular motility disturbances (including a case description of ophthalmoplegia internuclearis anterior occurring in conjunction with dissociated deficits of semicircular canal function)]. Klin Monatsbl Augenheilk. 1923;70:213–235. Reprinted with permission.

Abducting saccades were not overtly slowed, and all other eye movements were intact. The abduction defect could not be overcome with the vestibulo-ocular maneuver. Serial MRIs were negative until nearly two years after symptom onset, when a well-demarcated lesion in the region just above and posterior to the right third nerve nucleus (Fig. 21.3) was found. MR spectroscopy was inconclusive but did not support the presence of neoplastic tissue.

Figure 21.2 Mild limitation of abduction of the right eye on rightward gaze is suggested by the slight temporal scleral showing in the right eye (Also see color insert.)

A subsequently obtained eye movement recording demonstrated normal vertical gaze range (Fig. 21.4) and saccades. Only minimal asymmetries of horizontal saccadic velocities were noted: abducting saccades of the right eye were slightly slower than the left but largely remained in the normal velocity range (Fig. 21.5). Vestibulo-ocular responses were normal, while esodeviation, limited abduction, and secondary deviation of the left eye were confirmed (Fig. 21.4).

Approximately 2.5 years into the course of illness, the patient reported that his visual symptoms were unchanged but that for several months he had noted mild weakness of his left leg and arm after exertion. The only change in his eye movements was a small increase of the esodeviation in primary gaze to 10 prism diopters. However, he also demonstrated subtle weakness of the left arm and leg. The upperand lower-extremity reflexes were brisk bilaterally, and a Babinski sign was present on the left. There were no sensory deficits, cerebellar dysfunction, or facial asymmetries. The jaw jerk was hypoactive. MRIs of the cervical and thoracic spinal cord were normal. A subsequent lumbar puncture yielded no evidence for an inflammatory, infectious, or malignant process.

DISCUSSION

Lutz’s postulate of a prenuclear abducens palsy was based on incorrect assumptions of the anatomical pathways controlling horizontal gaze in the pons (Fig. 21.1). Thus, “posterior INO of Lutz” does not exist in the originally proposed manner. However, there are reports of midbrain and pontine lesions causing prenuclear abduction deficits.2,3 Thus the question arises: how could prenuclear innervational abnormalities produce an isolated unilateral abduction deficit? Two mecha- nisms—impaired prenuclear facilitation of abduction and excessive innervation of the antagonistic medial rectus—could lead to this finding. Each of these mechanisms has two inherent submechanisms: sixth nerve underfunction may be due to (1) increased prenuclear

inhibitory influences or (2) impairment of facilitation. Medial rectus overactivity, on the other hand, could reflect a loss of inhibitory influences on its subnucleus in the third nerve nuclear complex, or an increase of direct innervation.

Lutz’s1 proposed schematic implied a loss of prenuclear facilitation of the sixth nerve as the mechanism of “posterior INO,” but he did not present a case of his own. Instead, his manuscript referred to 3 patients previously reported by another author4 who had acquired unilateral horizontal gaze palsies. As their gaze palsies improved, adduction weakness resolved, but unilateral abduction deficits remained. Lutz stated that these cases “likely” had posterior INO.1 A contemporary case with such a presentation had a partial lesion of the paramedian pontine reticular formation (PPRF) and its projections to the sixth nerve nucleus.3 This resulted in the claim that “the posterior INO of Lutz is a disconnection of the fibers from the PPRF to the abducens nucleus that causes an abduction abnormality and spares adduction. The posterior INO of Lutz is extremely rare and depends on proof of preserved function of the sixth nerve during pursuit or vestibular eye movements.”5 Loss of prenuclear facilitation of abduction was also experimentally demonstrated by lidocaine-induced dysfunction of interneurons in the oculomotor nucleus projecting to the contralateral sixth nerve nucleus (Fig. 21.6). This inactivation of oculomotor internuclear neurons induced weakness of contralateral abduction6 in experimental animals. However, the ipsilateral location of our patient’s lesion above the level of the third nerve

A

Figure 21.4 Gaze plot obtained approximately two years into the course of illness. During viewing of a visual target with the right eye (left eye covered) (A), there is limited abduction of the right eye (gray). Also note the secondary deviation of the left eye (black). During viewing of a visual target with the left eye (right eye covered) (B), there is a right esophoria of about 10º.

Peak velocity (deg/s)

Duration (ms)

Saccades to Left

600

Peak velocity

500

400

300

200

0

Amplitude (˚)

nucleus and the absence of other eye movement disturbances preclude these two mechanisms as satisfactory explanations of his isolated, mild abduction deficit. Similarly, the theoretical mechanism of increased prenuclear inhibition of the sixth nerve does not seem to apply to our case. Inhibitory projections from one PPRF to its counterpart have been postulated,7 but such connections are more likely to be concerned with the dynamic control of saccades.

Horizontal gaze disturbances, on the other hand, are well documented in midbrain and diencephalic lesions corresponding with the phenomena of convergence excess,2 horizontal gaze paresis,8,9 thalamic esotropia,10 and pseudo–sixth nerve palsies.11,12 This raises the question of whether increased facilitation of the medial rectus or loss of inhibition of this muscle could

produce a picture of mild abducens weakness. In this context, ascending inhibitory projections from the PPRF to contralateral medial rectus motoneurons have been proposed13,14 but are not supported by anatomical studies.15

In prior reports of unilateral abduction weakness in conjunction with midbrain and diencephalic lesions,11,12 all patients had associated vertical gaze disturbances, and some also had convergence-retraction nystagmus. In a detailed study of ocular motor disturbances associated with lesions in the mesencephalo–diencephalic region,12 the laterality of abduction deficits corresponded with the vertical distance from the third nerve nucleus: lesions above the mesencephalo–diencephalic junction resulted in contralateral abduction weakness, while lower lesions produced ipsilateral deficits,

CN III

OIN

CN VI

AIN

PONS

Figure 21.6 Schematic summary of important anatomical connections between the oculomotor nucleus (CN III), which contains medial rectus motoneurons supplying the medial rectus (MR) muscle, and the abducens nucleus (CN VI), which contains abducens motoneurons that supply the lateral rectus (LR) muscle. The abducens nucleus also contains abducens internuclear neurons (AIN) that project to contralateral medial rectus motoneurons (synapse not shown). The oculomotor nucleus also contains oculomotor internuclear neurons (OIN) that project to the contralateral abducens nucleus. Experimental inactivation of OIN (arrow) causes contralateral abduction weakness.

suggesting that an inhibitory descending pathway for convergence may decussate in the subthalamic region.

A small lesion just above and posterior to the third nerve nucleus has been shown to produce a complete ipsilateral abduction deficit (“pseudoabducens palsy”) in conjunction with vertical gaze limitations and con- vergence-retraction nystagmus on attempted abduction (Case 5).12 The latter abnormalities were attributed to involvement of structures within the interstitial nucleus of Cajal and the rostral interstitial nucleus of the medial longitudinal fasciculus.12 Our patient’s lesion was located more posteriorly, sparing anatomical structures contributing to vertical gaze. His mild abduction weakness may be explained by only partial disruption of an inhibitory pathway to the medial rectus subnucleus. He manifested no other lesions or disease processes that could explain his esotropia. Thus, he may represent the first case of a supranuclear palsy of abduction with a well-defined radiological lesion lacking associated ocular motor deficits. Measurements of the dynamic properties of abnormal eye movements have not been performed in previously reported cases. However, in contrast to persistently diminished peak

saccadic velocities in chronic central sixth nerve palsies,16 our patient’s saccades remained essentially normal. He also showed no overt abnormalities of convergence, suggesting that the presumptive mechanism of loss of inhibitory input to the medial rectus does not produce a picture of convergence excess.

Numerous important questions regarding the nature of our patient’s disease process and the involved pathway(s) remain unanswered. The responsible lesion was radiologically silent for an extended period of time, and the patient is manifesting new neurological problems that have no imaging correlate. He may suffer from a demyelinating disorder such as multiple sclerosis, but supportive evidence for this diagnosis is presently lacking.

In summary, we present a case of isolated prenuclear abduction weakness associated with a midbrain lesion. It fulfills Lutz’s predictions of the existence of such a syndrome, but not his conjecture of a pontine lesion location. As his anatomical model was incorrect and prenuclear abduction deficits occur with diencephalic, midbrain, and pontine lesions, the syndrome of “posterior INO of Lutz” should be abandoned. Further studies are required to test several possible hypotheses to account for prenuclear abduction deficits.

ACKNOWLEDGMENTS This research was supported by National Institutes of Health grant EY06717, the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, and the Evenor Armington Fund (to Dr. Leigh).

References

1.Lutz A. Ueber die Bahnen der Blickwendung und deren Dissoziierung (nebst Mitteilung eines Falles von Ophthalmoplegia internuclearis anterior in Verbindung mit Dissoziierung der Bogengänge) [On ocular motor pathways and dissociated ocular motility disturbances (including a case description of ophthalmoplegia internuclearis anterior occurring in conjunction with dissociated deficits of semicircular canal function)]. Klin Monatsbl Augenheilk. 1923;70:213–235.

2.Keane JR. The pretectal syndrome. Neurology. 1990;40:684–690.

3.Bogousslavsky J, Regli F, Ostinelli B, Rabinowicz T. Paresis of lateral gaze alternating with so-called posterior internuclear ophthalmoplegia. A partial paramedian pontine reticular formation-abducens nucleus syndrome. J Neurol. 1985;232:38–42.

4.Priestley-Smith. Bilateral deviation of the eyes.

Ophthalmology Hospital Reports. 1879;9:22.

5.Walsh TJ, ed. Neuroophthalmology: Clinical Signs and Symptoms. 3rd ed. Philadelphia, PA: Lea & Febiger; 1992.

6.Clendaniel RA, Mays LE. Characteristics of antidromically identified oculomotor internuclear neurons during vergence and versional eye movements. J Neurophysiol. 1994;71:1111–1127.

7.Pierrot-Deseiligny C. Circuits oculomoteurs centraux. Rev Neurol. 1985;141:349–370.

8.Zackon DH, Sharpe JA. Midbrain paresis of horizontal gaze. Ann Neurol. 1984;16:495–504.

9.Masdeu JC, Rosenberg M. Midbrain-diencephalic horizontal gaze paresis. J Clin Neuroophthalmol. 1987;7:227–234.

10.Gomez CR, Gomez SM, Selhorst JB. Acute thalamic esotropia. Neurology. 1988;38:1759–1762.

11.Namer IJ, Oeztekin MF, Kansu T, Zileli T. Pseudo- sixth-nerve palsy with thalamo-mesencephalic junction lesion. Report of two cases. Neuroophthalmology. 1990;10:69–72.

12.Pullicino P, Lincoff N, Truax BT. Abnormal

vergence with upper brainstem infarcts.

Pseudoabducens palsy. Neurology. 2000;55: 352–358.

13.Thömke F, Hopf HC, Krämer G. Internuclear ophthalmoplegia of abduction: clinical and electrophysiological data on the existence of an abduction paresis of prenuclear origin. J Neurol Neurosurg Psych. 1992;55:105–111.

14.Thömke F, Hopf HC. Abduction paresis with rostral pontine and/or mesencephalic lesions: pseudoabducens palsy and its relation to the so-called posterior internuclear ophthalmoplegia of Lutz. BMC Neurology. 2001;1:4.

15.Büttner-Ennever JA: The extraocular motor nuclei: organization and functional neuroanatomy. In Büttner-Ennever JA, ed. Neuroanatomy of the Oculomotor System, Volume 151 (Progress in Brain Research). Amsterdam, the Netherlands: Elsevier; 2006:95–126.

16.Wong AMF, McReelis K, Sharpe JA. Saccade dynamics in peripheral vs central 6th nerve palsies. Neurology. 2006;66:1390–1398.

ABSTRACT

Divergence insufficiency is characterized by acquired, comitant, uncrossed diplopia at distance, but little or no deviation at near. Ductions are full with no evidence of abducens palsies. Our objective was to describe the association of hereditary spinocerebellar ataxia (SCA) and divergence insufficiency using a retrospective case review. We identified 6 patients with divergence insufficiency and spinocerebellar ataxia. All patients had a family history of acquired impaired balance, all patients had gaze-evoked nystagmus, and 4 had evidence of cerebellar atrophy on neuroimaging. Five patients were managed with corrective prisms, while 1 required extraocular muscle surgery. We found that acquired uncrossed horizontal diplopia at distance, but not near, occurs in patients with SCA as a result of divergence insufficiency. In most patients, the esodeviations were small and were managed easily with prisms. The clinical findings implicate predominant midline cerebellar dysfunction in our patients as the likely cause of their divergence insufficiency.

Divergence insufficiency is characterized by five criteria1: (1) acquired uncrossed horizontal diplopia at distance, but not near; (2) a comitant esotropia at distance;

(3) full ductions; (4) normal abducting saccades, with no signs of abducens palsies; and (5) reduced or absent fusional divergence. The diplopia may be intermittent and, like the esotropia, improve on lateral gaze.2

Unfortunately, the terms divergence insufficiency (DI) and divergence paralysis (DP) are used interchangeably, despite the fact that the definition of “paralysis” is “the complete loss of function of one or more muscle groups.” 3 In 1935, Bruce4 distinguished between “divergence insufficiency,” in which otherwise healthy patients develop sudden-onset esotropia at distance, and “divergence paralysis,” which is associated with underlying neurological diseases. DI can be distinguished from DP, which occurs as a result of bilateral abducens palsies in patients with severe head injuries, intracranial hypertension from other causes, intracranial hypotension, brainstem tumors, craniocervical junction abnormalities, and Fisher’s syndrome.5 Patients with DP usually have bilateral abduction defects, horizontal diplopia at distance, and quantitatively slowed abducting saccades. Occasionally, DI can be difficult to distinguish from DP, particularly in those patients recovering from DP who go through a phase during which the esotropia becomes comitant with full ductions, mimicking DI; however, abducting saccades are quantitatively slowed.6

Generally, DI occurs in patients who appear to be otherwise neurologically normal; however, occasionally it is reported with Chiari I malformations,7 midline cerebellar degeneration,8 and, rarely, sedation (diazepam). The association of DI and hereditary spinocerebellar degeneration is not well known. The purpose of this study is to report the association of DI with autosomal dominant spinocerebellar ataxia (SCA) in 6 patients and discuss their management.

CASE REPORTS

Patient 1

A 54-year-old man complained of episodes of intermittent diplopia that had generally occurred in the evenings during the previous year. Gradually the episodes increased in frequency. Also, he complained of progressive difficulty with his balance. His mother had impaired balance that began in her 60s, and his 68-year-old brother had a similar balance disorder. Neither he nor his family members had a history of strabismus.

With myopic correction his visual acuity was 20/20 in each eye. His eye movements were full, but he had gaze-evoked nystagmus. He was orthophoric at near but had a comitant 4 prism diopter esotropia at distance. The remainder of his eye exam was normal. His neurological exam revealed mild dysarthria and a wide-based gait. MRI of the brain was normal. His diplopia resolved with Fresnel prisms.

Over the next five years, the patient’s ataxia progressed, preventing him from working. His esotropia increased to 20 prism diopters at distance and 12 prism diopters at near. He was able to fuse 20 prism diopters at near through a bifocal, so bimedial rectus recession of 3.5 mm was performed for the distance angle esotropia. Postoperatively, he was orthophoric at near with a 3 prism diopter esophoria at distance, and had no diplopia. However, over the next two years, he regressed to a constant 6 prism diopter esotropia at distance, but remained orthophoric at near. The right medial rectus was re-recessed to 6 mm from the original site of insertion, and orthophoria was again achieved. At his most recent visit he complained of intermittent diplopia alleviated by tilting his head forward; examination revealed a 2 prism diopter esophoria at distance.

Patient 2

A 50-year-old woman had intermittent diplopia for the previous two years. Also, she complained of poor balance and frequent falls. Her father, paternal grandfather, and two paternal uncles had balance disorders; all experienced onset of symptoms in their 40s and had frequent falls.

Examination revealed vision correctable to 20/20 in each eye. The patient had full versions but upbeat nystagmus in primary gaze that worsened on up-gaze; also, she had horizontal gaze-evoked nystagmus. She was orthophoric at near but had a 10 prism diopter, comitant esotropia at distance. The remainder of her eye exam was normal. Neurological exam revealed a wide-based gait and inability to perform tandem gait. A brain MRI demonstrated midline cerebellar atrophy

and an incidental frontal venous angioma. Her diplopia resolved with 3 prism diopters of baseout Fresnel prism on each spectacle lens.

Patient 3

An 80-year-old woman with a 10-year history of diplopia complained of difficulty with balance and frequent falls. Family history was significant for a grandmother with a gait disturbance and balance difficulty. Her visual acuity was 20/30 OD and 20/25 OS. She had gazeevoked nystagmus to each side; she had a 2 prism diopter esotropia at distance and a 6 prism diopter exophoria at near. The remainder of the exam was remarkable for bilateral nuclear sclerotic cataracts. Neurological exam demonstrated bilateral finger-nose ataxia, dysdiadochokinesis, and a wide-based gait. Neuroimaging was not performed.

She was given baseout prisms. Over the next eight years, her distance esotropia increased to 6 prism diopters, but her symptoms were relieved with stronger prisms.

Patient 4

A 36-year-old homemaker complained of unsteady gait and visual distortion that she had experienced for the previous five months. The visual distortion progressed over a few weeks to frank, horizontal diplopia. She said she swayed, as if she were on a boat. Her paternal grandmother had a gait disturbance, beginning at age 40, that caused disability by age 80.

Her corrected visual acuity was 20/20 in each eye. She had full versions, but had horizontal gaze-evoked nystagmus with a small, superimposed torsional component. She had a comitant 4 prism diopter esotropia at distance but was orthophoric at near. The remainder of the eye exam was normal. Neurological examination was normal; specifically, her gait, station, balance, and cerebellar testing were normal. An MRI demonstrated mild midline cerebellar atrophy (Figure 22.1).

Her diplopia resolved with a 2 baseout Fresnel prism over each eye. She has remained asymptomatic with the same prisms for the past five years.

Patient 5

A 64-year-old man complained of intermittent diplopia, present for approximately 20 years. He had difficulty with his balance over the same time period. Otherwise, he was healthy and took no medication. His father had impaired balance.

His visual acuity was 20/20 with each eye. He had horizontal gaze-evoked nystagmus. His versions were limited symmetrically in all fields of gaze, but his saccadic

Figure 22.1 T1 weighted sagittal MRI demonstrating midline cerebellar atrophy.

velocities appeared normal; the restriction was conjugate and minimal. He was orthophoric at near but had a 4 to 6 prism diopter esotropia at distance. The remainder of the eye exam was unremarkable except for red-green color blindness and a small right epiretinal membrane. Neurological examination revealed poor balance and difficulty with tandem gait, but no appendicular ataxia. MRI revealed subtle cerebellar atrophy. Fresnel prisms relieved the patient’s diplopia adequately; he was lost to long-term follow-up.

Patient 6

A 64-year-old business analyst complained of an intermittent, horizontal diplopia for two years. Over the same time period, he reported worsening balance. His history was complicated by episodic dysarthria that lasted minutes and was attributed to transient ischemic attacks. He was treated with antiplatelet medication and had been free of the dysarthric episodes for the previous six months. His family history was significant for a balance disorder and tremor affecting his mother, maternal grandfather, and a maternal uncle. Examination revealed best-corrected vision of 20/20 in each eye. He had obliquely downward-beating nystagmus on lateral gaze in each direction. He had a small exophoria at near with a variable 6 to 8 prism diopter esotropia at distance. The remainder of his ophthalmic exam was unremarkable. His neurological exam revealed a wide-based gait with difficulty performing tandem gait. He had finger-to-nose ataxia and

dysdiadokinesis. An MRI revealed subtle midline cerebellar atrophy. DNA testing for known mutations associated with autosomal dominant SCA was negative. His diplopia resolved with a 2 prism diopter baseout Fresnel prism on each spectacle lens.

DISCUSSION

All 6 of our patients presented with diplopia at distance only, caused by divergence insufficiency; none had hyperopic esotropia, and, surprisingly, none was diagnosed with cerebellar degeneration before presentation. All had symptoms or signs, or both, of predominant midline cerebellar dysfunction; all had strong family histories of gait ataxia or disequilibrium, or both (Table 22.1). In the absence of other causes for cerebellar disease, these findings strongly suggested they had familial spinocerebellar degeneration (i.e., autosomal dominant cerebellar ataxia [SCA]). All were treated empirically with vitamin E as an antioxidant. Genetic testing was not performed in 5 of our patients, mainly for financial reasons: 2 of the 5 patients were offered testing but declined, and 1 had a negative test. Saccadic velocities were measured in 1 patient and were normal.

The association of divergence insufficiency with cerebellar dysfunction is reported sparsely in the literature. Cunnigham9 and Lepore10 each described patients with divergence insufficiency and ataxia; in those with no obvious intracranial pathology, their symptoms were attributed to stroke or microvascular ischemic changes determined by neuroimaging. Jacobsen11 reported divergence insufficiency in 2 patients with “cerebellar degenerations” but did not give further details. Versino’s group12 described 6 patients with cerebellar degeneration, gait ataxia, and esophoria but did not report formal ocular motility examinations. The esodeviations in their patients were measured at distance only; also, they did not report family histories. Lastly, Ohyagi’s group2 reported DI in 3 members of a single Japanese family with SCA3.

Multiple gene loci are established for a number of SCA subtypes, but many remain to be identified. Thus, while a positive genetic test is helpful in diagnosis, a negative result does not exclude hereditary disease.13

Radiological evidence of cerebellar atrophy is not always present, particularly early in the course of the disease. Additional study will be necessary to determine whether specific subtypes of SCA may lead to a greater predisposition to DI.

It is unclear whether DI is caused by underaction of divergence or overaction of convergence. The cerebellum has a significant role in controlling vergence. The flocculus has neurons that discharge in relation to the

165 INSUFFICIENCY DIVERGENCE