OBJECTIVE: Sub-Tenon anesthesia is a form of local anesthetic techniques used in ophthalmic procedures, especially in cataract surgery. Few studies in our environment have reported the effects of sub-Tenon anesthesia on akinesia and analgesia as well as optimum volumes of anesthetic agents that are required for effective analgesia and akinesia. The objective of this study is to determine and compare the level of analgesia and akinesia and the effect of ocular compressions after sub-Tenon injection of 2 mL versus 3 mL of xylocaine among patients booked for cataract surgery in the University of Ilorin Teaching Hospital (UITH).
METHODS: A cross-sectional comparative study among cataract patients booked for surgery in the Department of Ophthalmology at UITH was carried out from March 2017 to August 2017. A total of 200 cataract patients that met the inclusion criteria were recruited into the study over 6 months. Lists of cataract patients booked for surgery formed the sampling frame. Questionnaires were administered to obtain information on sociodemographic, ocular symptoms, and other histories. Visual acuity was checked, and ocular examination was done with a pen-torch, ophthalmoscope, and slit-lamp examination with 78D. Tonometry and optic nerve assessments were done to exclude any patient with preexisting glaucoma or suspicious disc. About 200 patients were randomly allocated into one of two volume groups (Group 1 had 2 mL sub-Tenon xylocaine injection whereas Group 2 had 3 mL); level of analgesia and akinesia was checked 12 min and 15 min, respectively.
RESULTS: The age range was 20-107 years; mean age for Group 1 was 63.8 ± 12.64, whereas the mean age of Group 2 was 64.14 ± 14.14. There was a slight female preponderance given a M:f of 1:1.4 and more than half of the patients presented with right eye (RE) cataract. Levels of analgesia 12 min after sub-Tenon injections in both groups were similar. However, two patients were found to have severe pain in Group 1, and no patients had severe pain in Group 2. The level of akinesia which was assessed 15 min after injection in both groups was found to be significantly better in Group 2.
CONCLUSIONS: There was a slight female preponderance with about two-third of the total patients being female and the percentage of females who had no pain was more than the male, more than 50% of the patients had RE cataracts. Sub-Tenon anesthesia whether with 2 mL or 3 mL led to a statistically significant rise in intraorbital pressure (IOP); however, with ocular compression, the IOP was found to decrease below the preinjection pressure in both groups. Levels of analgesia were similar in the two groups, whereas akinesia was statistically better in the group that had 3 mL injection.

Parkinson\'s disease is caused by a selective vulnerability and cell loss of dopaminergic neurons of the Substantia Nigra pars compacta and, consequently, striatal dopamine depletion. In Parkinson\'s disease therapy, dopamine loss is counteracted by the administration of L-DOPA, which is initially effective in ameliorating motor symptoms, but over time leads to a burdening side effect of uncontrollable jerky movements, termed L-DOPA-induced dyskinesia. To date, no efficient treatment for dyskinesia exists. The dopaminergic and serotonergic systems are intrinsically linked, and in recent years, a role has been established for pre-synaptic 5-HT1a/b receptors in L-DOPA-induced dyskinesia. We hypothesized that post-synaptic serotonin receptors may have a role and investigated the effect of modulation of 5-HT4 receptor on motor symptoms and L-DOPA-induced dyskinesia in the unilateral 6-OHDA mouse model of Parkinson\'s disease. Administration of RS 67333, a 5-HT4 receptor partial agonist, reduces L-DOPA-induced dyskinesia without altering L-DOPA\'s pro-kinetic effect. In the dorsolateral striatum, we find 5-HT4 receptor to be predominantly expressed in D2R-containing medium spiny neurons, and its expression is altered by dopamine depletion and L-DOPA treatment. We further show that 5-HT4 receptor agonism not only reduces L-DOPA-induced dyskinesia, but also enhances the activation of the cAMP-PKA pathway in striatopallidal medium spiny neurons. Taken together, our findings suggest that agonism of the post-synaptic serotonin receptor 5-HT4 may be a novel therapeutic approach to reduce L-DOPA-induced dyskinesia.

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We report the third case of FADS due to biallelic DOK7 variants, which further strengthens the association of DOK7 with this lethal phenotype and lack of genotype phenotype correlation.

Progressive supranuclear palsy (PSP) is associated with several clinical variants defined based on ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction, although little is known about how these features progress over time. We aimed to assess the evolution of these core clinical features across variants and assess baseline clinical and neuroimaging predictors of progression.
Ninety-three PSP patients were recruited by the Neurodegenerative Research Group, Mayo Clinic, and underwent two visits 1-year apart, with baseline MRI and [18F]flortaucipir PET. We compared baseline and annualized rates of clinical change on the PSP Rating Scale (total, ocular motor, gait/midline scores) and Montreal Cognitive Assessment, across PSP-Richardson\'s, PSP-Cortical and PSP-Subcortical variants and assessed relationships between rates of change and baseline regional imaging.
Ocular motor scores differed across groups at baseline and follow-up, with lowest scores observed in PSP-subcortical, but no differences were observed in rate of change across groups. PSP Rating Scale total and gait/midline scores differed across groups at follow-up and in rates of change, with PSP-subcortical showing the least impairment and slowest progression. Greatest cognitive impairment was observed in PSP-Cortical. Sample size estimates for treatment trials differed across PSP variants. Greater baseline flortaucipir uptake, but not volume, of midbrain and motor cortex correlated with faster rates of clinical decline.
The PSP Rating Scale and its subscores might be useful markers for the prognostic stratification of PSP variants. Flortaucipir imaging at baseline may help predict rate of decline.

Parkinson\'s disease (PD) is a motor disorder charactertised by altered neural activity throughout the basal ganglia-thalamocortical circuit. Electrical deep brain stimulation (DBS) is efficacious in alleviating motor symptoms, but has several notable side-effects, most likely reflecting the non-specific nature of electrical stimulation and/or the brain regions targeted. We determined whether specific optogenetic activation of glutamatergic motor thalamus (Mthal) neurons alleviated forelimb akinesia in a chronic rat model of PD. Parkinsonian rats (unilateral 6-hydroxydopamine injection) were injected with an adeno-associated viral vector (AAV5-CaMKII-Chrimson-GFP) to transduce glutamatergic Mthal neurons with the red-shifted Chrimson opsin. Optogenetic stimulation with orange light at 15 Hz tonic and a physiological pattern, previously recorded from a Mthal neuron in a control rat, significantly increased forelimb use in the reaching test (p < 0.01). Orange light theta burst stimulation, 15 Hz and control reaching patterns significantly reduced akinesia (p < 0.0001) assessed by the step test. In contrast, forelimb use in the cylinder test was unaffected by orange light stimulation with any pattern. Blue light (control) stimulation failed to alter behaviours. Activation of Chrimson using complex patterns in the Mthal may be an alternative treatment to recover movement in PD. These vector and opsin changes are important steps towards translating optogenetic stimulation to humans.

To compare the efficacy and safety of sub-tenon block to peribulbar block with respect to analgesia, akinesia, and complications.
It is an observational study conducted at a government hospital in Karnataka. Seventy patients who came to the ophthalmology OPD for small-incision cataract surgery (SICS) under local anesthesia were included in the study. The participants were divided into two groups of 35 as per the surgeon. The pain was evaluated at the time of administration of the block, during the surgery, and during the postoperative period of 4 h. Akinesia was noted in both the groups and the time of onset of akinesia was noted. Any complications associated with the block such as chemosis or subconjunctival hemorrhage were also noted. Statistical analysis was done using PSS version 25.0, where P < 0.05 was considered significant.
The baseline pain score was higher in the peribulbar group (1.57). The onset of akinesia was faster in sub-tenons (90.34 s). Complete akinesia was achieved in 82.9% of patients after peribulbar block. There was no significant difference in complications in both groups.
Sub-tenons block is an effective and safer technique of ocular anesthesia for SICS. It can be considered as an alternative to the conventional peribulbar block for SICS.

Parkinson\'s disease (PD) is known to affect the brain motor circuits involving the basal ganglia (BG) and to induce, among other signs, general slowness and paucity of movements. In upper limb movements, PD patients show a systematic prolongation of movement duration while maintaining a sufficient level of endpoint accuracy. PD appears to cause impairments not only in movement execution, but also in movement initiation and planning, as revealed by abnormal preparatory activity of motor-related brain areas. Grasping movement is affected as well, particularly in the coordination of the hand aperture with the transport phase. In the last fifty years, numerous behavioral studies attempted to clarify the mechanisms underlying these anomalies, speculating on the plausible role that the BG-thalamo-cortical circuitry may play in normal and pathological motor control. Still, many questions remain open, especially concerning the management of the speed-accuracy tradeoff and the online feedback control. In this review, we summarize the literature results on reaching and grasping in parkinsonian patients. We analyze the relevant hypotheses on the origins of dysfunction, by focusing on the motor control aspects involved in the different movement phases and the corresponding role played by the BG. We conclude with an insight into the innovative stimulation techniques and computational models recently proposed, which might be helpful in further clarifying the mechanisms through which PD affects reaching and grasping movements.

OBJECTIVE: We compared the effects of sub-Tenon\'s capsule anesthesia (STA) and trans-Tenon\'s capsule retrobulbar anesthesia (TTRBA) in 68 patients with epiretinal membrane.
METHODS: Either STA or TTRBA was induced with 3 mL of lidocaine (2%) before vitrectomy combined with phacoemulsification and aspiration (phacovitrectomy). Akinesia was evaluated by range of eye movement (ROEM) in upward, downward, nasal, and temporal directions at 4, 10, and 30 minutes after injection. Analgesia was evaluated with a visual analogue pain score, which ranged from 0 to 10.
RESULTS: The mean cumulative ROEMs were 1.44±1.02 corneal diameters (CDs) at 4 minutes, 0.55±0.76 CDs at 10 minutes, and 0.26±0.33 CDs at 30 minutes in patients who received STA; these values were 0.39±0.35 CDs at 4 minutes, 0.22±0.30 CDs at 10 minutes, and 0.13±0.29 CDs at 30 minutes in patients who received TTRBA. At both 4 and 10 minutes, the cumulative ROEMs in all directions, as well as the temporal ROEMs, were significantly larger in patients who received STA than in patients who received TTRBA. Pain scores did not significantly differ between groups at any time point.
CONCLUSIONS: STA and TTRBA produced identical degrees of analgesia, but akinesia was slower in patients who received STA. TTRBA might be preferable for patients undergoing brief vitrectomy.

Arthrogryposis multiplex congenita (AMC) describes a group of conditions characterized by the presence of non-progressive congenital contractures in multiple body areas. Scoliosis, defined as a coronal plane spine curvature of ≥10 degrees as measured radiographically, has been reported to occur in approximately 20% of children with AMC. To identify genes that are associated with both scoliosis as a clinical outcome and AMC, we first queried the DECIPHER database for copy number variations (CNVs). Upon query, we identified only two patients with both AMC and scoliosis (AMC-SC). The first patient contained CNVs in three genes (FBN2, MGF10, and PITX1), while the second case had a CNV in ZC4H2. Looking into small variants, using a combination of Human Phenotype Ontogeny and literature searching, 908 genes linked with scoliosis and 444 genes linked with AMC were identified. From these lists, 227 genes were associated with AMC-SC. Ingenuity Pathway Analysis (IPA) was performed on the final gene list to gain insight into the functional interactions of genes and various categories. To summarize, this group of genes encompasses a diverse group of cellular functions including transcription regulation, transmembrane receptor, growth factor, and ion channels. These results provide a focal point for further research using genomics and animal models to facilitate the identification of prognostic factors and therapeutic targets for AMC.