Ocular motor abnormalities in progressive supranuclear palsy

Eleven patients, 7 males and 4 females, of progressive supranuclear palsy (PSP) were examined neuro-otologically for the purpose of elucidating the characteristics of ocular motor abnormalities. All cases were admitted to our hospital and age at onset was from 52 to 71 years old, duration of illness was 2 to 11 years. Range of voluntary eye movements and abnormal eye movements including nystagmus were examined on naked eyes and with electronystagmography (ENG). Smooth pursuit movements and saccadic eye movements were tested both horizontally and vertically by using visual tracking method with ENG recordings. Optokinetic nystagmus test and caloric test with visual suppression test were also performed. These neurotological examinations were made repetitively in 5 cases and their progressions were observed. Vertical gaze palsy and convergence palsy were observed in all cases as the initial symptom. In this study downward gaze was more severely disturbed than upward gaze. Using ENG, saccadic eye movements (saccades) were disturbed earlier than smooth pursuit movements. Hypometric saccades and decreased saccadic velocity were common abnormalities. In the later stage of the disease, horizontal eye movements were also disturbed. In four cases bilateral adduction palsy was added to vertical gaze paralysis so that the lesion of the MLF to oculomotor nucleus was suggested to exist. These voluntary eye movements were worsened gradually as the disease progressed. By using ENG we could find so called abnormal eye movements more frequently than the previous reports. Eight patients demonstrated horizontal gaze nystagmus, and rebound nystagmus were observed in four cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Whipple's disease mimicking progressive supranuclear palsy: the diagnostic value of eye movement recording

Treatable causes of parkinsonian syndromes are rare; Whipple's disease is one of them. A patient is described who presented with a parkinsonian syndrome and abnormal vertical gaze. Measurement of eye movements showed marked slowing of upward saccades, moderate slowing of downward saccades, a full range of voluntary vertical eye movements, curved trajectories of oblique saccades, and absence of square wave jerks. These features, atypical of progressive supranuclear palsy, suggested the diagnosis of Whipple's disease, which was subsequently confirmed by polymerase chain reaction analysis of intestinal biopsy material. Precise measurement of the dynamic properties of saccadic eye movements in parkinsonian patients may provide a means of identifying treatable disorders.     

Supranuclear vertical gaze palsy: bilateral thalamo-mesencephalic lesions demonstrated by MRI

The exact location for the major control center of the vertical gaze, which is referred to as rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), has been documental in a few autopsy studies. However, CT in some of the case reports of vertical gaze palsy have not clearly delineated this nucleus and its nearby complex anatomical structures. Discrete small, bilateral, symmetric infarcts in the thalamo-mesencephalic junction were demonstrated by MRI in a 59-year-old female patient who had sustained vertical gaze palsy over a period of nine years. Neurological examination revealed severe supranuclear combined downward and upward vertical gaze palsy, incomplete convergence, and slight limitation in adduction of the right eye. There was neither ptosis, pupillary disturbance, nor any further abnormalities of horizontal eye movements. The vertical vestibulo-ocular reflex was maintained, being similar to the other reported cases of vertical gaze palsy. MRI has advantages over CT in demonstrating lesions in the thalamo-mesencephalic junction in the cases of vertical gaze palsy, because clearer sagittal images can be obtained.     

Functional paralysis of horizontal gaze

A 52-year-old steelworker displayed a consistent defect in leftward voluntary gaze across the midline. Both fast (saccadic) and slow (pursuit) eye movements were affected. Neuro-ophthalmologic evaluation revealed no additional neurologic or ophthalmologic deficit. Pupilary miosis occurred during leftward gaze attempt, indicating that the gaze palsy was due to spasm of the near reflex. Special maneuvers during clinical eye movement testing disclosed full ability to make normal horizontal fast and slow eye movements despite the apparent defect in "voluntary" leftward gaze.     

A case of left third nerve palsy and contralateral vertical gaze palsy with medial midbrain infarction]

An 81-year-old man developed oculomotor nerve palsy of the left eye and vertical gaze palsy of the right eye due to left medial midbrain infarction. His left eyelid was ptotic and the pupil was dilated. His right eye showed normal horizontal movement and Bell's phenomenon was preserved although the oculocephalic reflex was incomplete. There were no other abnormal neurological findings. The brain MRI revealed a high-intensity lesion in left medial midbrain on T2 weighted image. This lesion involved the oculomotor nerve nucleus, the interstitial nucleus of Cajal, and the rostral intersititial nucleus of the medial longitudinal fasciculus (riMLF). We thought that upward gaze palsy of the right eye was resulted from the infarction of the left riMLF or disruption of the axonal collateral of upward gaze fibers in the left oculomotor nucleus. Downward gaze palsy was resulted from the damage of the downward gaze fibers before their decussation, or the damage of the left interstitial nucleus of Cajal. This case provides evidence that unilateral lesion of the midbrain could cause contralateral vertical gaze palsy.     

Apraxia of eyelid closure in a patient with progressive supranuclear palsy]

We reported a 68-year-old man with progressive supranuclear palsy who present with apraxia of eyelid closure. He showed horizontal and vertical supranuclear ophthalmoplegia, neck dystonic posture, pseudobulbar palsy and subcortical dementia. He opened his eyes almost all day long except for sleeping. His spontaneous blinking was noted at less than 1 per a minute. Although he closed his eyes reflexively, he could not close his eyes by verbal command. He occasionally closed his eyelids by using both hands. The surface electromyographic (EMG) findings revealed that the frequency of frontal muscle contraction did not decrease, and rather increased during verbal command to close his eyes. The contraction frequency of orbicularis oculi muscle did not increase by the command of voluntary eyelid closure. It is suggested that abnormal contractions of frontalis and orbicularis oculi muscles which are correlated in eyelid closing and opening might contribute to the apraxia of eyelid closure.     

Oral baclofen increases maximal voluntary neuromuscular activation of ankle plantar flexors in children with spasticity due to cerebral palsy.

Although spasticity is a common symptom in children with cerebral palsy, weakness may be a much greater contributor to disability. We explore whether a treatment that reduces spasticity may also have potential benefit for improving strength. Ten children with cerebral palsy and spasticity in the ankle plantar flexor muscles were treated with oral baclofen for 4 weeks. We tested voluntary ability to activate ankle plantar flexor muscles using the ratio of the surface electromyographic signal during isometric maximal voluntary contraction to the M-wave during supramaximal electrical stimulation of the tibial nerve and tested muscle strength using maximal isometric plantar flexion torque. Mean maximal voluntary neuromuscular activation increased from 1.13 +/- 1.02 to 1.60 +/- 1.30 ( P < .05) after treatment, corresponding to an increase in 9 of 10 subjects. Mean maximal plantar flexion torque did not change. We conjecture that antispasticity agents could facilitate strength training by increasing the ability to voluntarily activate muscle.     

Calretinin inputs are confined to motoneurons for upward eye movements in monkey

Motoneurons of extraocular muscles are controlled by different premotor pathways, whose selective damage may cause directionally selective eye movement disorders. The fact that clinical disorders can affect only one direction, e.g., isolated up‐/downgaze palsy or up‐/downbeat nystagmus, indicates that up‐ and downgaze pathways are organized separately. Recent work in monkey revealed that a subpopulation of premotor neurons of the vertical eye movement system contains the calcium‐binding protein calretinin (CR). With combined tract‐tracing and immunofluorescence, the motoneurons of vertically pulling eye muscles in monkey were investigated for the presence of CR‐positive afferent terminals. In the oculomotor nucleus, CR was specifically found in punctate profiles contacting superior rectus and inferior oblique motoneurons, as well as levator palpebrae motoneurons, all of which participate in upward eye movements. Double‐immunofluorescence labeling revealed that CR‐positive terminals lacked the γ‐aminobutyric acid (GABA)‐synthesizing enzyme glutamate decarboxylase, which is present in inhibitory afferents to all motoneurons mediating vertical eye movements. Therefore, CR‐containing afferents are considered to be excitatory. In conclusion, a strong CR input is confined to motoneurons mediating upgaze, which derive from premotor pathways mediating saccades and smooth pursuit, but not from secondary vestibulo‐ocular neurons in the magnocellular part of the medial vestibular nucleus. The functional significance of CR in these connections is unclear, but it may serve as a useful marker to locate upgaze pathways in the human brain. J. Comp. Neurol. 521:3154–3166, 2013. © 2013 Wiley Periodicals, Inc.     

Paresis of lateral gaze alternating with so-called posterior internuclear ophthalmoplegia. A partial paramedian pontine reticular formation-abducens nucleus syndrome

Summary A patient with multiple myeloma developed gaze paresis to the left with slowed saccades and gaze-paretic nystagmus, which alternated with abduction palsy in the left eye (with preserved oculocephalic deviation) and dissociated adducting nystagmus in the right eye, suggesting so-called posterior internuclear ophthalmoplegia. At autopsy multiple small infarcts were found with partial destruction of the left paramedian pontine reticula formation (PPRF) extending towards the abducens nucleus, which was involved only in its inferior pole. The medial longitudinal fasciculus and other oculomotor structures were spared. It is suggested that slowing of all ipsilateral saccades with gaze-paretic nystagmus corresponded to partial destruction of the PPRF, and that intermitted abduction palsy in the ipsilateral eye with adduction nystagmus in the fellow eye was due to intermittant dysfunction of the abducens nucleus. Involvement of voluntary saccades, pursuit movements and vestibulo-ocular responses may be dissociated in partial lesions of the abducens nucleus.     

Intra- and interrater reliabilities of the Myotonometer when assessing the spastic condition of children with cerebral palsy

The purposes of this study were to assess intra- and interrater reliabilities by novice users of the Myotonometer (Neurogenic Technologies, Inc., Missoula, MT), a portable electronic device that quantifies muscle tone (stiffness) and paresis, in assessing children with cerebral palsy. Two raters used the Myotonometer to assess the biceps brachii and medial gastrocnemius muscles of 10 children with spastic-type cerebral palsy. Muscles were measured in a relaxed state and during a voluntary isometric contraction. Intraclass correlation coefficients and repeatability coefficients were calculated for each muscle and for each condition (relaxed and contracted). Intrarater reliabilities ranged from 0.82 to 0.99 (biceps brachii muscles) and 0.88 to 0.99 (medial gastrocnemius muscles). Interrater reliabilities ranged from 0.74 to 0.99 (biceps brachii muscles) and 0.84 to 0.99 (medial gastrocnemius muscles). Repeatability coefficients indicated a 98% level of agreement between raters across all conditions. Novice users of the Myotonometer, with few exceptions, had high to very high intra- and interrater reliabilities for measurements of the biceps brachii and medial gastrocnemius muscles of children with spastic-type cerebral palsy.     

A hypothetical scheme for the brainstem control of vertical gaze

OBJECTIVES: To develop a hypothetical scheme to account for clinical disorders of vertical gaze based on recent insights gained from experimental studies. METHODS: The authors critically reviewed reports of anatomy, physiology, and effects of pharmacologic inactivation of midbrain nuclei. RESULTS: Vertical saccades are generated by burst neurons lying in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). Each burst neuron projects to motoneurons in a manner such that the eyes are tightly coordinated (yoked) during vertical saccades. Saccadic innervation from riMLF is unilateral to depressor muscles but bilateral to elevator muscles, with axons crossing within the oculomotor nucleus. Thus, riMLF lesions cause conjugate saccadic palsies that are usually either complete or selectively downward. Each riMLF contains burst neurons for both up and down saccades, but only for ipsilateral torsional saccades. Therefore, unilateral riMLF lesions can be detected at the bedside if torsional quick phases are absent during ipsidirectional head rotations in roll. The interstitial nucleus of Cajal (INC) is important for holding the eye in eccentric gaze after a vertical saccade and coordinating eye-head movements in roll. Bilateral INC lesions limit the range of vertical gaze. The posterior commissure (PC) is the route by which INC projects to ocular motoneurons. Inactivation of PC causes vertical gaze-evoked nystagmus, but destructive lesions cause a more profound defect of vertical gaze, probably due to involvement of the nucleus of the PC. Vestibular signals originating from each of the vertical labyrinthine canals ascend to the midbrain through several distinct pathways; normal vestibular function is best tested by rotating the patient's head in the planes of these canals. CONCLUSIONS: Predictions of a current scheme to account for vertical gaze palsy can be tested at the bedside with systematic examination of each functional class of eye movements.     

Pathophysiological mechanisms in cerebral palsy.

To investigate some of the pathophysiological mechanisms in cerebral palsy, surface electromyograms (EMG) were recorded from pairs of flexor/extensor muscles during both voluntary and passive flexion/extension of upper and lower limbs of 20 patients. Elbow, knee, or ankle joint angles were measured simultaneously, as well as the force required to flex/extend the limbs passively at frequencies of 0.1--1.0 Hz. In addition, single motor units were recorded from the first dorsal interosseous muscles of six of the patients. Almost all patients showed resistance to passive movements (hypertonia). This hypertonia did not necessarily impair voluntary flexion/extension movements if alternating EMG activity was maintained in at least one of the pairs of flexor/extensor muscles involved in the movement. In six severly involved patients, there was a complete breakdown in the reciprocal relationship between reciprocally acting pairs of flexor/extensor motoneurones, which resulted in synchronous activation (co-contractions) of flexor/extensor muscles during both voluntary and passive movements. In these patients the hyperactive segmental reflex added to the disabling effects of co-contractions during voluntary movements. Single motor units recorded from patients with dystonic movements were recruited with variable delays (2--10 s) and usually discharged intermittently at high frequencies (60--120/s). This abnormla motor unit discharge pattern may relate to pathology of the basal ganglia.     

Dorsal midbrain syndrome: clinical and oculographic findings

We report clinical and oculographic findings in seven patients with the dorsal midbrain syndrome (Parinaud's syndrome). All presented with limited upward voluntary gaze and convergence nystagmus with attempted upward voluntary gaze. Quantitative analysis of vertical eye movements documented characteristic abnormalities of saccades with relative preservation of reflex eye movements (ie, vestibular, optokinetic, and visual-vestibular). Vertical saccade velocity was only slightly decreased in five patients with tumors, indicating that the vertical burst neurons in the mesencephalic reticular formation and their efferent pathways to the oculomotor neurons were minimally damaged. On the other hand, two patients with probable brainstem encephalitis exhibited marked slowing of vertical saccades, indicating that the burst neurons, or their efferent pathways to the oculomotor neurons, were severely damaged.     

Voluntary vertical nystagmus

A patient with hypertropia caused by fourth-nerve palsy manifested primary position oscillations characteristic of voluntary nystagmus. This benign condition must be kept in mind even when dealing with primary position vertical nystagmus to avoid extensive and potentially dangerous investigations.     

A case of amyotrophic lateral sclerosis with disturbance of vertical ocular movement responding to thyrotropin releasing hormone (TRH)

A 64-year-old woman who had amyotrophic lateral sclerosis (ALS) with disturbance of vertical ocular movement was presented. She was admitted to our hospital with progressive dysphagia, dysarythria and weakness of the extremities. Neurological examinations revealed disturbance of vertical ocular movement with normal doll's eye phenomenon (supranuclear origin), bulbar palsy, muscle weakness of the extremities, extensor plantar signs, and fasciculations of the costal and interosseal muscles. EMG studies showed denervation potentials, and muscle biopsy demonstrated group atrophy, fiber type grouping and small angular fibers. TRH injections resulted in improvement of disturbance of vertical ocular movement, but no effect was seen on the weakness of the limb. There was about 20 Japanese cases with disturbance of ocular movement in ALS, but it was rare to see ocular movement disorder from the early stage of ALS. The pathophysiology of ocular movement disorder in ALS has been thought to be due to supranuclear origin, i.e., the disturbance in the pathway from the frontal cortex to the mesencephalon. In this case, TRH might effect at some point of the frontomesencephalic pathway.     

Influence of target size on vertical gaze palsy in a pathologically proven case of progressive supranuclear palsy.

We document a new oculomotor phenomenon in a patient with pathologically proven progressive supranuclear gaze palsy (PSP), namely that vertical gaze excursion improves with larger pursuit targets. We used computerised video-oculography during vertical smooth pursuit eye movements (SPEM) of circular targets of diameter 0.16 degrees and 16 degrees, sinusoidally oscillating at 0.08 Hz (peak-to-peak amplitude 49 degrees). Increasing target size improved vertical gaze excursion from 10 degrees to 25 degrees. There was no concomitant increase in slow phase eye velocity. The findings could be explained by a potentiation of the position control mechanism of pursuit by target size due to increased activation of brainstem pursuit-optokinetic pathways and to higher order attentional mechanisms. This observation may be useful in the clinical assessment of PSP patients with severe neck rigidity in whom the doll's head-eye manoeuvre cannot be performed by comparing the degree of vertical gaze palsy during smooth pursuit testing between at least two differently sized targets and observing whether there is a larger excursion in response to a large target such as a newspaper.     

帕金森病发病危险因素的研究

目的 探讨帕金森病发病的危险因素。方法 利用病例对照研究方法对１００例ＰＤ患者和１００例年龄及性别相匹配的对照组进行分析，并对７２例ＰＤ和６６例对照者的载脂蛋白Ｅ基因型进行检测。结果 发现引起ＰＤ发病的危险因素包括不良环境暴露，幼年期的居住地，脑外伤，阳性家族史及农业劳动等；同时发现ａｐｏＥ等位基因频率在ＰＤ和本研究的对照组间分布无显著性差异。     

EFFECTS OF BODY ORIENTATION IN SPACE ON TONIC MUSCLE ACTIVITY OF PATIENTS WITH CEREBRAL PALSY

This study was designed to determine whether tonic activity of selected muscles of patients with cerebral palsy changed in response to changes in orientation of the body in space. Surface electrodes measured electromyographic activity of the low-back extensor, hip adductor and ankle plantar-flexor muscles when the body was at 0 degree (upright) and 30 degrees (recline) relative to the vertical. Muscle activity did change in response to body orientation, and was less in the upright position.     

"Abducens neuromyotonia" with partial oculomotor paralysis]

Paroxysmal involuntary spasms of extraocular eye muscles which can lead to reversible pathological eye positions and limitations of eye movements are etiologically heterogenous. Despite the diagnostic difficulty, they are important as a neurological sign because of the usually good response to treatment. We report on a patient with the unusual combination of ocular neuromyotonia with brief paroxysmal tonic lateral deviation of the left eye and a concomitant partial third nerve palsy. The paroxysmal episodes disappeared with carbamazepine therapy. Possible pathomechanisms are discussed.     

Vertical oculomotor apraxia and memory loss

A case of vertical oculomotor apraxia with severe memory loss and hypokinetic inertia is described in a 34-year-old woman who was taking oral contraceptives. The eye movement disorder was limited to paralysis of voluntary vertical saccades; pursuit movements, reflex eye movement, and horizontal saccades were normal. Random involuntary vertical saccades documented by electronystagmography qualified this as a true apraxia. Similar cases from the literature have in common involvement of both medial thalami, a localization supported in this case by distinctive abnormalities on CAT scan. The clinical course suggested acute infarction, possibly due to embolism, in a territory supplied by the thalamosubthalamic paramedian arteries.