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Objective: To study the pathogenesis of congenital nystagmus., Methods: We observed the ultrastructure of extraocular muscles from congenital nystagmus patients with transmission electron microscope., Results: As to extraocular muscle in congenital nystagmus of jerky type, there wre myofibrillae perpendicular to axes of myocytes within the myocytes in the quick phase side. This kind of myofibrillae had the structure of sarcomeres. In slow phase side, there were perpendicular myofibrillae in the periphery of myocytes and the adjacent nuclear region. There was dense nuclear matrix within myocytes and the membrane of nucleus was intact. With regard to pendular type of congenital nystagmus, there was no perpendicular myofibrillae within myocytes. The myofibrillae parallel to the axes of myocytes were arranged disorderly. The length of sarcomeres in different myofibrillar was not identical. Within myocytes of different types of congenital nystagmus, there was a large amount of mitochondria, in which the inner crest was arranged disorderly and there was vacuole formation., Conclusion: This study demonstrates that congenital nystagmus has the pathological basis of ultrastructural changes.

Clinical and MRI investigations were carried out on 27 patients with acquired pendular nystagmus in an attempt to delineate possible sites of lesions responsible for pendular nystagmus and mechanisms underlying the frequent ocular disconjugacy of this nystagmus. The aetiologies were multiple sclerosis (n = 21), brainstem stroke (n = 3) and other neurological conditions. In at least 59% of the patients, pendular nystagmus appeared > 1 year after the first symptom of the disease. Patients MRIs were characterized by multiple areas of abnormal signal and were analysed statistically to identify areas where lesions overlapped significantly between patients. Statistically significant overlap occurred in areas containing the red nucleus, the central tegmental tract, the medial vestibular nucleus and the inferior olive. Patients with horizontal pendular nystagmus showed predominantly pontine lesions whereas patients with torsional pendular nystagmus showed predominantly medullary involvement. The nystagmus was conjugate in 15 patients and disconjugate in amplitude or direction in 12. Internuclear ophthalmoplegia or asymmetrical visual acuity occurred in similar proportions in both groups. Patients with conjugate pendular nystagmus had a higher incidence of symmetrical, "mirror image' lesions on MRI than patients with disconjugate nystagmus. The abundance of abnormal MRI signals in our sample suggests that large or multiple structural lesions may be required to elicit pendular nystagmus, predominantly in the pons but also in the midbrain and medulla. The involvement of structures projecting to the inferior olive supports the hypothesis that oscillatory properties of olivary neurons causes the rhythm of pendular nystagmus. The delay observed between the onset of the underlying disease and the pendular nystagmus supports a mechanism operating via neural deafferentation. Disconjugancies in pendular nystagmus cannot be explained on the basis of the associated internuclear ophthalmoplegias nor on the basis of asymmetrical visual acuity. The association between symmetrical MRI lesions and conjugate nystagmus suggests that asymmetrical damage to brainstem structures concerned with binocular alignment may underlie disconjugate pendular nystagmus.

In this study, the possibility of whether basophilic deposits adhered to the cupulas in the semicircular canals was investigated histologically. Results indicated that basophilic deposits were present in all three cupulas of the semicircular canals. The overall incidence of basophilic deposits in the superior, lateral and posterior semicircular canal cupulas was 26%, 41% and 37%, respectively. The incidence of basophilic deposits bound to the cupulas increased with age. The possible origin of these basophilic deposits on the cupulas and the increased incidence of basophilic deposits with increasing age are discussed.

A 29-year-old woman with bitemporal hemianopia persisting after a suprasellar germinoma was resected twelve years previously had brief periods of pendular seesaw nystagmus after blinks and horizontal or vertical saccades. Nystagmus may have been suppressed during fixation, and escaped only when fixation was interrupted by blinks or saccades.

A 55-year-old woman had paroxysms of vertigo and visual blurring associated with complex combined torsional, horizontal, and vertical nystagmus. These episodes occurred regularly at 2-minute intervals, each attack lasting for 15 seconds. Between attacks, there was a much finer asymptomatic nystagmus whose components were in the opposite direction to those associated with the paroxysmal attacks. A brain MRI revealed an arteriovenous malformation in close proximity to the left vestibular nucleus, with evidence of previous bleeding. Caloric testing demonstrated a left-sided vestibular paresis. We suggest that neurons in this patient's damaged left vestibular nucleus are usually underactive but regularly produce pathologic brief bursts of hyperactivity causing episodic reversal and gross exacerbation of her resting nystagmus. Treatment with low-dose carbamazepine was successful in abolishing both the paroxysms of nystagmus and the symptoms of vertigo and visual disturbance.

The ultrastructure of the extraocular muscles of patients affected by congenital nystagmus is still to be defined. Specimens obtained from patients suffering from either oculomotor congenital nystagmus or nystagmus associated with strabismus were studied and compared with specimens obtained from patients enucleated for various pathologies but not affected by any oculomotor system disorder. The scleral myotendinous junction and the muscle body (venter) were examined. In both these areas, damaged muscle fibers were found. 'Mitochondrial cores' and concentric myofibrils characterized the extraocular muscles of the patients with oculomotor congenital nystagmus. In the extraocular muscles of the patients affected by nystagmus associated with strabismus we also found mitochondria with concentric cristae surrounding a highly electron-dense spherical body and numerous, large rods. In conclusion, these data indicate that both contractile and mitochondrial modifications might be signs of an altered muscle function and seem to indicate that oculomotor congenital nystagmus should be included among the list of oculomotor myopathies.

A patient with multiple sclerosis presented with oscillopsia due to an acquired pendular nystagmus that was dissociated in amplitude, being larger in the eye with a relative afferent pupil defect. Eye movement recordings showed an unusual dissociation in nystagmus frequency as well. Although the frequencies differed, the eyes remained phase locked as the right eye was oscillating exactly twice as fast as the left eye.

Purpose: The purpose of this study is to describe the heterogeneous phenotype of individuals with an unusual type of albinism--minimal pigment oculocutaneous albinism., Methods: Nine patients with minimal pigment oculocutaneous albinism were identified and followed for up to 11 years. The criteria were the presence of oculocutaneous albinism in association with low hairbulb tyrosinase activity in the patient and disparate activity in the parents with one parent having normal activity and the other having low tyrosinase activity. Changes in skin, hair, and ocular pigment were followed as the patients matured. As a measure of ocular pigment, iris transillumination and macular transparency were graded according to a previously published scheme., Results: Patients were born with white scalp hair and skin, and nystagmus developed. Visual acuity was reduced to 20/50 to 20/200 for the group, but in one patient vision improved with maturity. Irides were blue. In seven patients, iris pigment developed, which was detected by transillumination with slit-lamp biomicroscopy, including the one patient with improved visual acuity. All patients had foveal hypoplasia, and melanin pigment in the fundi could not be detected by clinical examination. Visual acuity in the group did not correlate directly with the presence or development of iris transillumination or macular transparency. The pedigrees were consistent with an autosomal recessive inheritance pattern., Conclusion: This unique type of oculocutaneous albinism has heterogeneous clinical features. Minimal pigment oculocutaneous albinism appears to represent a new type of tyrosinase-related oculocutaneous albinism (OCA1MP).

A 43 year old man presented with decreased sensitivity in the left side of the face and both upper limbs, and with upbeat nystagmus and skew deviation. MRI demonstrated a well defined lesion compatible with an infarct in the left side of the medulla, caudal and ventral to the vestibular nuclei, possibly involving the most caudal of the perihypoglossal nuclei, the nucleus intercalatus. Ocular motor studies, using an infrared system, showed that the nystagmus slow phase decayed exponentially, suggesting a failure of integration for vertical eye movements. Vertical integration might, therefore, be performed partly in the nucleus intercalatus.

Ten patients with canal paresis of central origin and ten patients with peripheral canal paresis were studied using MRI of the brainstem to identify lesions within the central vestibular pathways. In the central group, the magnitude of the canal paresis was generally lower than in the peripheral group and removal of fixation had little effect on the nystagmic response. In the peripheral group, removal of fixation enhanced the nystagmus and lessened the discrepancy between the two ears. Statistical processing of the MRI showed that in the central group significant spatially coincident lesions occurred within the medial vestibular nucleus, lateral vestibular nucleus and proximal portion of the vestibular fascicle.

We describe a patient with a dissociated vertical nystagmus and an internuclear ophthalmoplegia. The vertical nystagmus consisted of a left downward nystagmus with a synchronous right intorting nystagmus when the patient looked down and to the left. This rare type of nystagmus has been described both in isolation and in association with an internuclear ophthalmoplegia. Previous authors postulated a lesion in the midbrain in the region of the medial longitudinal fasciculus. In our patient, a discrete midbrain infarction was demonstrated on magnetic resonance imaging in the hypothesized location, thus providing supportive anatomical evidence for a vertical gaze coordination pathway in the region of the medial longitudinal fasciculus.

We describe an electro-oculographic study of upbeat nystagmus in 4 patients, with neuropathological correlation in one. All patients had lesions in the pontine tegmentum. The electro-oculographic data may be explained by imbalanced vertical vestibular or smooth pursuit eye movement control. The nystagmus stopped or reversed direction during convergence or in supine head positions. We propose that changes in the intensity or direction of upbeat nystagmus that are induced by convergence or changes in head position, are caused by vertical imbalance in the otolithic-ocular reflex, when superimposed on an imbalanced vestibulo-ocular reflex (VOR). Imbalance of the otolithic-ocular reflex and the vertical VOR are caused by damage in the pontomedullary tegmentum.

To establish the difference of mechanism between irritative and paralytic nystagmus, alterations of Na-K-ATPase and succinic dehydrogenase activity in the vestibular sensorineural elements were investigated for 20 guinea pigs, and glucose uptake of the vestibular nuclei for 13 guinea pigs were measured by the [14C]-2-deoxy-D-glucose method. Irritative and paralytic nystagmus were experimentally provoked by introducing K+ into the perilymphatic space. From the results it was concluded that irritative nystagmus is provoked by increased excitability of vestibular sensory cells, while paralytic nystagmus is provoked by decreased excitability. However, the direction of nystagmus was eventually decided by the tonus imbalance between the bilateral vestibular nuclei. The ipsilateral vestibular nucleus was predominant during irritative nystagmus, while the contralateral vestibular nucleus was predominant during paralytic nystagmus.

Macular coloboma is a congenital retinochoroidal defect of the macular region. It is a bilateral, nonprogressive condition that is associated with decreased visual acuity and nystagmus. A case of a 14-year-old boy with an unusual presentation of extensive macular colobomata is described. Location of the lesions differentiated this case from true or typical retinochoroidal colobomata. Differential diagnosis also includes postinflammatory scarring.

Surgery for a horizontal face turn or tilt in patients with congenital nystagmus began in 1953 and has been modified frequently since then. There are few published reports stating the frequency of or surgical guidelines for the treatment of a vertical or torsional head position due to congenital nystagmus and associated null point. To address this issue a questionnaire was sent to all members of the American Association for Pediatric Ophthalmology and Strabismus. Most respondents see one or two cases of vertical head posture yearly and use observation as their primary therapy. When surgery is indicated, a graded bilateral vertical rectus recession or combined vertical rectus recession-resection procedure are usually done. Most respondents see no cases of torsional head posture yearly, and an overwhelming majority observe these patients. No one surgical procedure was advocated by most of the responding surgeons.

A 24-year-old woman had bilateral pendular nystagmus, foveal hypoplasia, 360-degree peripheral retinal rosettes, and hypoplastic ora serrata of nongenetic origin. Kinetic perimetry revealed a generalized constriction of the field. Flicker perimetry revealed general depression of the critical flicker frequencies in the entire field. A slight increase of the threshold for light sensitivity after dark adaptation was noted from 10 to 30 degrees. Haidinger brush phenomenon was abnormal. Color vision was normal. The electroretinogram revealed mild abnormalities in the photopic flicker response. The visual-evoked response, recorded by local macular stimulation, was abnormal. The relationship of foveal hypoplasia to peripheral retinal rosettes in this case may have been caused by an intercurrent infection during the late stages of embryogenesis.

Electro-oculographic recordings of dissociated vertical (oblique and upbeat) nystagmus were carried out in a patient in coma due to vascular lesions. Based on the clinical and neuropathological findings, it was suggested that dissociated vertical (oblique and upbeat) nystagmus in a patient in coma can be caused by bilateral lesions in the brachium pontis.

Brain-stem pause neurons (PNs) are inhibitory neurons which cease their tonic firing about 20 ms prior to the quick phase of horizontal vestibular nystagmus in either direction. One group of nystagmus-related burst neurons just rostral to the abducens nucleus exhibits a burst of spikes before and during the quick phase to the ipsilateral side--excitatory burst neurons (EBNs). The present study supported the conclusion that PNs project to, and tonically inhibit EBNs during the slow phase and that the burst of activity of EBNs at the quick phase is partly caused by the abrupt release from pauser inhibition. The evidence leading to this conclusion is: simultaneous recording of PNs and EBNs showed close alternation of firing; PNs were antidromically activated from the EBN region; systematic microstimulation tracks within the EBN region showed an antidromic activation pattern of low threshold sites separated by high threshold sites consistent with PN axonal branching in the EBN region; during the nystagmus slow phase there were positive field potentials in the EBN region, followed by an abrupt negative deflection whose onset was synchronous with the last pauser spike; when single PN spikes were used to trigger averages of extracellular field potentials in the EBN region (postspike averaging), a consistent short-latency positivity was observed. This study shows an additional connection in the premotor neural network responsible for the generation of the quick phase of horizontal vestibular nystagmus.

Two sisters who manifested downbeat nystagmus at the early stage of leukodystrophy are reported. The younger sister whose onset was at the age of 20, deteriorated rapidly to the vegetative state, and died of acute pneumonia 7 years after. Her downbeat nystagmus was observed only during the early 2 years of the course of her disease. The histopathological study on her brain enabled a diagnosis of sudanophilic leukodystrophy which demonstrated overall gliosis of white matter in the cerebrum and severe depopulation of Purkinje cells in the cerebellum, particularly in the vermis. The elder sister's onset was at the age of 29 and deteriorated rapidly to akinetic mutism. Her downbeat nystagmus was observed only during the first year of the course of her disease. For over 10 years she has been at the vegetative state. CT-scan of her brain demonstrates low density areas in the white matter of the cerebrum and in the vermis of the cerebellum. These two cases showed similar clinical signs and courses of their diseases, which were spontaneous nystagmus, early changes of personality and intelligence, and extra-pyramidal sign and later rapid deterioration of the stage of akinetic mutism. Histopathologically these cases are suspected as having an identical hereditary etiology of sudanophilic leukodystrophy. In these cases it is noted that downbeat nystagmus was the early sign of the disease.

Abnormal eye movements described as ocular bobbing are most often encountered in the setting of pontine vascular disease. This report deals wih the onset and course of ocular bobbing in a young woman who had encephalitis confirmed by biopsy. Unusual eye movements developed during progressive deterioration of brain and brain stem function which led to coma. The eye movements occurred spontaneously and could also be triggered by cutaneous stimulation of the face, head, extremities, and auditory canals. The patient recovered fully over a period of several months.

A case report on a 26 years old woman, who was admitted for a pontobulbar vascular accident. She took oral anticoncipients since 10 years without any control. Vertebral angiography confirmed the basilar artery thrombosis. Otoneurologic investigation was three times performed. The cochleovestibular alterations were in accordance with the neurologic signs and demonstrated the level and extension of the pathologic process. The autopsy confirmed the clinical diagnosis.

Monozygotic twin sisters were afflicted by a chronic progressive neurological disease characterized by slurred speech, nystagmus and oculogyral spasms as well as further extrapyramidal and lower motor neuron abnormalities. At autopsy severe loss of nigral and craniospinal motor neurons was noted. In the nuclei of most nerve cell types of the central and peripheral nervous system, roundish inclusion bodies of 3 to 10 microns in diameter were found. Ocular pathology revealed the presence of identical inclusion bodies in the ganglion cells and ganglion cell loss in the posterior retina. Retinal astrocytosis and loss of myelinated axons of the optic nerve were interpreted as reactive features. No inclusions were found in the retinal pigment epithelium. Careful neuro-ophthalmological studies of the first-degree relatives revealed low b-wave of the ERG with other slight aberrations. These were assumed to represent either a carrier or a subclinical state of this presumably inherited disorder.

Two patients had upward nystagmus on forward gaze before they died with acute caudal brainstem dysfunction. Bilateral dorsal paramedian damage in the rostral medulla, involving the perihypoglossal nuclei, was probably the critical lesion responsible for upbeat nystagmus.

Opsoclonus is an involuntary eye movement disorder in which there are chaotic, usually conjugate, multidimensional saccadic eye movements. In this paper 2 cases of opsoclonus are reported, as a paraneoplastic phenomenon in association with oat cell carcinoma of the lung. It has previously been hypothesized that opsoclonus results from dysfunction of a group of premotor neurons in the brainstem called omnipause neurons. We describe the location of these cells in man by homology with animal studies, and describe the light microscopic appearance of these neurons in the 2 cases of opsoclonus. Although these neurons appeared normal it is still possible that their function was disturbed as a result of metabolic or neurotransmitter abnormalities.

Chronic states of methylmercurialism were induced in squirrel monkey subjects. Principal neurological signs included ataxia, abnormal gait, incoordination and amaurosis. Although slight to moderate vacuolization occurred in supporting cell layers of the cristae and maculae, receptor cell function was essentially normal. Except for a lowered cold threshold, bithermal caloric-induced nystagmus was not significantly different from control values. Pre and postrotatory (Barany chair) tests revealed a reduction only in frequency related variables. The development of spontaneous and positional nystagmus (sometimes with eyes open) coupled with the behavioral signs and the evidence of normal receptor response suggested cerebellar dysfunction. Severe pathologic changes were present in the cerebral cortex, but no lesions were found in the cerebellar cortex. Substantial neuronal degeneration and gliosis, however, were observed in several subcortical nuclei, including cerebellar and vestibular nuclei.

Two patients with amyotrophic lateral sclerosis proved postmortem had nystagmus in addition to typical clinical signs of motor neuron disease. The first patient had gaze-evoked rotatory nystagmus that was followed by horizontal nystagmus in the primary position with supranuclear paresis of horizontal gaze and upgaze. The second patient had rotatory nystagmus that was evoked by lateral gaze, with normal range of eye movements. Nystagmus is so rare in motor neuron disease that these observations may imply another disease, but postmortem examination did not provide any other explanation. These two cases add to the increasing evidence that motor neuron disease comprises a heterogeneous group of disorders.

Three patients who had slowly alternating skew deviation are described; each had elements of the Sylvian aqueduct syndrome. This combination of signs supports a pretectal location for lesions associated with alternating skew movements. Postmortem examination of a patient who died of chronic herpes simplex encephalitis showed extensive demyelination and periaqueductal spongiform degeneration; there was preservation of the oculomotor and trochlear nuclei, the medial longitudinal fasciculus, vestibular nuclei, and the interstitial nucleus of Cajal bilaterally. The slowly alternating dysconjugate vertical movements bear a resemblance to both see-saw nystagmus and the ocular tilt response.

We examined a 73-year-old woman with the rare association of albinism and (presumably) congenital periodic alternating nystagmus. The mechanism of the nystagmus in this case is uncertain. Anomalous retinogeniculate pathways have been documented in albino animals. Periodic alternating nystagmus might occur in some patients with albinism if there are also anomalies in the pathways conveying visual information to the cerebellum and brainstem.

Abnormalities of optokinetic nystagmus are described in a patient with pathologically proven bilateral infarcts in the middle cerebral artery territories. There were no other central nervous system lesions. These abnormalities of eye movement are interpreted as indicating an inhibitory effect of the frontal eye fields upon the occipital lobes.

Clinical and neuropathological descriptions are given of four cases of an uncommon disease, characterised by simultaneous degeneration of the dentato-rubral and pallido-luysian systems. These four are compared with sixteen previously described cases, and the group as a whole is compared and contrasted with other multisystem degenerations, such as olivo-ponto-cerebellar atrophy and Friedreich's ataxia. A pathological feature described here for the first time is degeneration of the fastigio-vestibular system. Clinically, there are three main types of the disease; (1) an ataxo-choreoathetoid type, (2) a pseudo-Huntington type, and (3) a myoclonic-epileptic type. There are familial cases of types 2 and 3. Oculomotor disturbances, associated with atrophy of the brainstem tegmentum, are observed in cases of types 1 and 3.

A family exhibiting a leukocytic arylsulfatase A deficiency, probably inherited in an autosomal recessive manner, differed from patients with typical metachromatic leukodystrophy in that sulfatiduria was absent and there was readily detectable cerebroside sulfatase activity. To our knowledge, this family was unique in that there were no known members with metachromatic leukodystrophy and the only neurologic abnormality was progressive retinal pigment degeneration in the proband.

A 35-year-old man with aplastic anemia developed prominent downbeat nystagmus 80 days after receiving an allogeneic bone marrow transplant. A diagnosis of herpes simplex encephalitis was made which was confirmed by positive virus cultures at autopsy 1 week later. Routine pathologic examination of the brain stem revealed no lesions which would explain the downbeat nystagmus. Immunoperoxidase studies, however, revealed virus-infected neurones throughout the brain stem including the nuclei of the basis pontis, the superior olive, and nuclei of the spinal tracts of 5 and 10. The significance of "negative" pathologic brain stem findings in cases of downbeat nystagmus is discussed.

A quite unique patient aged 13, characterized by a combination of organoid nevus on the left scalp and subtotal cerebellar agenesis accompanied by hypoplasia of the pons and midbrain, was reported. Cardinal clinical features consisted of nonprogressive cerebellar manifestations including intention tremor and ataxia, speech and visual disturbance and mental retardation. An electronystagmogram demonstrated periodic alternating nystagmus. A clinical diagnosis of cerebellar agenesis in this case was made through the demonstration of characteristic features in metrizamide CT and midline sagittal tomography of metrizamide cisternography of the posterior fossa. An extensive review of the literature revealed three papers dealing with organoid nevus associated with various neurological abnormalities, but no single case with a similar combination of cutaneous organoid nevus and cerebellar agenesis had been reported.

In 6 previously asymptomatic patients the hypophysis (adenoma) hemorrhages developed suddenly with prompt severe signs of subarachnoidal hemorrhage or vision loss up to total blindness. Five patients were either operated via transfrontal approach or transnasal stereotaxic cryodestruction of the tumor was performed. One patient died before operation within 24h after admission. Of the 6 patients, 5 had the chromophobic hypophyseal adenomas. Of the 5 operated patients 4 remain in satisfactory conditions for 4 to 10 years. The success of the treatment in patients with hemorrhages into the asymptomatic hypophyseal tumors depends on prompt detection and urgent surgery.

The general roentgenogram of the cervical spine often shows manifold pathological alterations by patients without any clinical complaints. On the other hand, there are cervical vertigo and different symptoms caused by the cervical spine, its joints, muscles and ligaments without any X-ray manifestation. Nevertheless, some connections are assumed to exist between vertigo and alterations of the cervical spine an assumption supported especially by the frequently successful elimination of cervical troubles by chirotherapy. We compared the X-ray manifestations in patients complaining of vertigo with any and without any pathological proprioceptive cervical nystagmus provoked by examination according to Moser and revealed by electronystagmography. The extended posture of the cervical spine seems to point to a possible cause of vertigo. Likewise, some degenerative alterations seem to exercise a pathological effect, provoking cervical vertigo additionally if both effects are combined. Uncovertebral arthroses seem to have the same effect without occurring in combination with other effects. The general roentgenogram of the cervical spine in the sloping, lateral and anterior-posterior direction may consequently point to some possible causes of cervical vertigo.