Age- and sex-related oculomotor manifestation of dopamine deficiency in Segawa disease.

OBJECTIVE: To investigate the oculomotor manifestations of Segawa disease (SD), considered to represent mild dopamine deficiency and discuss their pathophysiological basis. METHODS: We recorded visually- (VGS) and memory-guided saccade (MGS) tasks in 31 SD patients and 153 age-matched control subjects to study how basal ganglia (BG) dysfunction in SD evolves with age for male and female subjects. RESULTS: SD patients were impaired in initiating MGS, showing longer latencies with occasional failure. Patients showed impaired ability to suppress reflexive saccades; saccades to cues presented in MGS were more frequent and showed a shorter latency than in control subjects. These findings were more prominent in male patients, particularly between 13 and 25 years. Additionally, male patients showed larger delay in MGS latency in trials preceded by saccades to cue than those unpreceded. CONCLUSIONS: The findings can be explained by a dysfunction of the BG-direct pathway impinging on superior colliculus (SC) due to dopamine deficiency. The disturbed inhibitory control of saccades may be explained by increased SC responsivity to visual stimuli. SIGNIFICANCE: Oculomotor abnormalities in SD can be explained by dysfunction of the BG inhibitory pathways reaching SC, with a delayed maturation in male SD patients, consistent with previous pathological/physiological studies.

A Rare Case of Meningitis Caused by Streptococcus gallolyticus subsp. pasteurianus in an Immunocompetent Young Adult.

Bacterial meningitis is a life-threatening condition that is mainly caused by Streptococcus pneumoniae and Neisseria meningitis. Although Streptococcus gallolyticus subsp. pasteurianus (Sgp) is also known to cause meningitis, its frequency is quite low, especially in adults. We herein report the first immunocompetent Japanese adult patient (20-year-old woman) with bacterial meningitis caused by Sgp. The patient showed dramatic improvement after antibiotic treatment. Although previous reports have described an association between Sgp infection and an immunosuppressive status, bowel and hepatobiliary diseases, or strongyloidiasis, our case did not demonstrate any of these conditions, suggesting that Sgp can cause meningitis even in young immunocompetent adults.

The Pathophysiology of Gilles de la Tourette Syndrome: Changes in Saccade Performance by Low-Dose L-Dopa and Dopamine Receptor Blockers.

AIM: To elucidate the pathophysiology of Gilles de la Tourette syndrome (GTS), which is associated with prior use of dopamine receptor antagonists (blockers) and treatment by L-Dopa, through saccade performance. METHOD: In 226 male GTS patients (5-14 years), we followed vocal and motor tics and obsessive-compulsive disorder (OCD) after discontinuing blockers at the first visit starting with low-dose L-Dopa. We recorded visual- (VGS) and memory-guided saccades (MGS) in 110 patients and 26 normal participants. RESULTS: At the first visit, prior blocker users exhibited more severe vocal tics and OCD, but not motor tics, which persisted during follow-up. Patients treated with L-Dopa showed greater improvement of motor tics, but not vocal tics and OCD. Patients with and without blocker use showed similarly impaired MGS performance, while patients with blocker use showed more prominently impaired inhibitory control of saccades, associated with vocal tics and OCD. DISCUSSION: Impaired MGS performance suggested a mild hypodopaminergic state causing reduced direct pathway activity in the (oculo-)motor loops of the basal ganglia-thalamocortical circuit. Blocker use may aggravate vocal tics and OCD due to disinhibition within the associative and limbic loops. The findings provide a rationale for discouraging blocker use and using low-dose L-Dopa in GTS.

Abnormal saccade profiles in hereditary spinocerebellar degeneration reveal cerebellar contribution to visually guided saccades.

OBJECTIVE: To study how the pathophysiology underlying hereditary spinocerebellar degeneration (spinocerebellar ataxia; SCA) with pure cerebellar manifestation evolves with disease progression using saccade recordings. METHODS: We recorded visually- (VGS) and memory-guided saccade (MGS) task performance in a homogeneous population of 20 genetically proven SCA patients (12 SCA6 and eight SCA31 patients) and 19 normal controls. RESULTS: For VGS but not MGS, saccade latency and amplitude were increased and more variable than those in normal subjects, which correlated with cerebellar symptom severity assessed using the International Cooperative Ataxia Rating Scale (ICARS). Parameters with significant correlations with cerebellar symptoms showed an aggravation after disease stage progression (ICARS > 50). The saccade velocity profile exhibited shortened acceleration and prolonged deceleration, which also correlated with disease progression. The main sequence relationship between saccade amplitude and peak velocity as well as saccade inhibitory control were preserved. CONCLUSIONS: The cerebellum may be involved in initiating VGS, which was aggravated acutely during disease stage progression. Dysfunction associated with disease progression occurs mainly in the cerebellum and brainstem interaction but may also eventually involve cortical saccade processing. SIGNIFICANCE: Saccade recording can reveal cerebellar pathophysiology underlying SCA with disease progression.

Early detection of cognitive decline in Alzheimer's disease using eye tracking.

Background: Patients with Alzheimer's disease (AD) are known to exhibit visuospatial processing impairment, as reflected in eye movements from the early stages of the disease. We investigated whether the pattern of gaze exploration during visual tasks could be useful for detecting cognitive decline at the earliest stage. Methods: Sixteen AD patients (age: 79.1 ± 7.9 years, Mini Mental State Examination [MMSE] score: 17.7 ± 5.3, mean ± standard deviation) and 16 control subjects (age: 79.4 ± 4.6, MMSE score: 26.9 ± 2.4) participated. In the visual memory task, subjects memorized presented line drawings for later recall. In the visual search tasks, they searched for a target Landolt ring of specific orientation (serial search task) or color (pop-out task) embedded among arrays of distractors. Using video-oculography, saccade parameters, patterns of gaze exploration, and pupil size change during task performance were recorded and compared between AD and control subjects. Results: In the visual memory task, the number of informative regions of interest (ROIs) fixated was significantly reduced in AD patients compared to control subjects. In the visual search task, AD patients took a significantly longer time and more saccades to detect the target in the serial but not in pop-out search. In both tasks, there was no significant difference in the saccade frequency and amplitude between groups. On-task pupil modulation during the serial search task was decreased in AD. The number of ROIs fixated in the visual memory task and search time and saccade numbers in the serial search task differentiated both groups of subjects with high sensitivity, whereas saccade parameters of pupil size modulation were effective in confirming normal cognition from cognitive decline with high specificity. Discussion: Reduced fixation on informative ROIs reflected impaired attentional allocation. Increased search time and saccade numbers in the visual search task indicated inefficient visual processing. Decreased on-task pupil size during visual search suggested decreased pupil modulation with cognitive load in AD patients, reflecting impaired function of the locus coeruleus. When patients perform the combination of these tasks to visualize multiple aspects of visuospatial processing, cognitive decline can be detected at an early stage with high sensitivity and specificity and its progression be evaluated.

Effect of subthalamic nucleus deep brain stimulation on visual scanning.

OBJECTIVE: Deep brain stimulation (DBS) can provide insights into the workings of the basal ganglia (BG) by interfering with their function. In patients with Parkinson's disease (PD) treated with DBS of the subthalamic nucleus, we studied the effect of DBS on scanning eye movements. METHODS: In the visual memory task, subjects viewed images of various complexities for later recall. In visual search tasks, subjects looked for and fixated one odd target ring, embedded among 48 Landolt rings, which either stood out or not from the distractors. We compared the parameters of scanning saccades when DBS was on and off. RESULTS: In the visual memory task, DBS increased the amplitude of saccades scanning simple but not complex drawings. In the visual search tasks, DBS showed no effect on saccade amplitude or frequency. CONCLUSIONS: Saccades when viewing simple images were affected by DBS since they are internally guided saccades, for which the involvement of BG is large. In contrast, saccades when viewing complex images or during visual search, made with the help of visual cues in the images (externally guided saccades) and less dependent on BG, were resistant to the effect of DBS. SIGNIFICANCE: DBS affects saccades differentially depending on the task.

Chemoenzymatic synthesis of amylose-grafted cellulose.

This paper reports the chemoenzymatic synthesis of an amylose-grafted cellulose. A maltoheptaose was chemically introduced to the amine-functionalized cellulose by reductive amination to produce the maltoheptaose-grafted cellulose. Then, the phosphorylase-catalyzed enzymatic polymerization of glucose 1-phosphate from the graft-chain ends on the cellulose derivative was performed, giving the amylose-grafted cellulose. The obtained material is shown to form gels and films. The dry and wet cycles of the materials were repeated.

Chemoenzymatic syntheses of amylose-grafted chitin and chitosan.

Amylose-grafted chitin and chitosan were synthesized by chemoenzymatic methods according to the following reaction manners. First, maltoheptaose was introduced to chitosan by a reductive amination using sodium cyanotrihydroborate in a mixed solvent of 1.0 mol/L aqueous acetic acid and methanol at room temperature to produce a maltoheptaose-grafted chitosan (1). The functionality of maltoheptaose to chitosan in 1 depended on reaction time. The phosphorylase-catalyzed enzymatic polymerization of R-D-glucose 1-phosphate was then performed from 1 to obtain amylose-grafted chitosan (2). Maltoheptaose-grafted chitin (3) was synthesized by N-acetylation of 1 using acetic anhydride in a mixed solvent of aqueous acetic acid and methanol. Then, synthesis of amylose-grafted chitin (4) was performed by the phosphorylase-catalyzed enzymatic polymerization under conditions the same as those for 2. The average DPs of amylose graft chains in 2 and 4 depended on the feed ratios of R-D-glucose 1-phosphate to maltoheptaose primers in 1 and 3.