Transcranial Direct Current Stimulation on Parkinson's Disease: Systematic Review and Meta-Analysis.

Background: Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson's disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD. Objective: Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms. Methods: A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were included. Results: Ten studies (n = 236) were included in meta-analysis and 25 studies (n = 405) in qualitative synthesis. The most frequently stimulated targets were dorsolateral prefrontal cortex and primary motor cortex. No significant effect was found among single targets on motor outcomes: Unified Parkinson's Disease Rating Scale (UPDRS) III - motor aspects (MD = -0.98%, 95% CI = -10.03 to 8.07, p = 0.83, I 2 = 0%), UPDRS IV - dyskinesias (MD = -0.89%, CI 95% = -3.82 to 2.03, p = 0.55, I 2 = 0%) and motor fluctuations (MD = -0.67%, CI 95% = -2.45 to 1.11, p = 0.46, I 2 = 0%), timed up and go - gait (MD = 0.14%, CI 95% = -0.72 to 0.99, p = 0.75, I 2 = 0%), Berg Balance Scale - balance (MD = 0.73%, CI 95% = -1.01 to 2.47, p = 0.41, I 2 = 0%). There was no significant effect of single vs. multiple targets in: UPDRS III - motor aspects (MD = 2.05%, CI 95% = -1.96 to 6.06, p = 0.32, I 2 = 0%) and gait (SMD = -0.05%, 95% CI = -0.28 to 0.17, p = 0.64, I 2 = 0%). Simple univariate meta-regression analysis between treatment dosage and effect size revealed that number of sessions (estimate = -1.7, SE = 1.51, z-score = -1.18, p = 0.2, IC = -4.75 to 1.17) and cumulative time (estimate = -0.07, SE = 0.07, z-score = -0.99, p = 0.31, IC = -0.21 to 0.07) had no significant association. Conclusion: There was no significant tDCS alone short-term effect on motor function, balance, gait, dyskinesias or motor fluctuations in Parkinson's disease, regardless of brain area or targets stimulated.

History of and Insights Into Spinal Cord Stimulation in Parkinson Disease.

BACKGROUND: Current available therapies for Parkinson disease (PD) have strong limitations, and patients usually present with refractory symptoms despite all efforts. Deep brain stimulation (DBS), which has been used in PD patients for decades (since 1987), has best indications for symptoms like tremor, motor fluctuations, or dyskinesia. However, postural instability and gait disturbances (PIGD) have restricted benefits with DBS. In 2009, spinal cord stimulation (SCS), a well-established therapy for chronic pain, has emerged as a potential alternative therapy that may help control unresponsive symptoms such as bradykinesia, PIGD, and freezing of gait. METHODS: The main studies regarding SCS in PD are reviewed here from the first studies in animal models to the latest clinical trials. CONCLUSIONS: Despite promising findings, the heterogeneity of methodologies used and small samples in human studies pose a challenging problem to be addressed in order to have robust clinical evidence to support SCS as a viable PD treatment.

Egg Model Training Protocol for Stereotaxic Neurosurgery and Microelectrode Implantation.

BACKGROUND: Neuroscience research uses neurosurgery in animal models for several experimental techniques. To our knowledge, there is no published method for small animal neurosurgery training. Based on the similar thickness of chicken eggshells and mouse, rat, and some small primate skulls, here we propose an egg model training protocol for stereotaxic surgery. MATERIALS AND METHODS: To perform training it was used a boiled egg and the same materials needed to perform stereotaxic neurosurgery in small animals. DISCUSSION: This protocol allows trainees in neuroscience research to become familiar with the microsurgery setting and learn neurosurgery techniques, such as craniotomy drilling, dura mater removal, and electrode implantation. CONCLUSION: Egg model suitably mimics animal neurosurgery for the replacement and sparing of animals intended for training in neurosurgical skills.

Morphometric analysis of NADPH diaphorase reactive neurons in a rat model of focal excitotoxic striatal injury.

Excitotoxicity is the major component in neuropathological conditions, related to harmful action of imbalanced concentrations of glutamate and its agonists in the nervous tissue, ultimately resulting in cell death. In the present study, we evaluated the effects of an acute striatal lesion induced by a focal N-methyl-D-aspartate (NMDA) microinjection on the morphometry of NADPH diaphorase-reactive neurons (NADPH-d+ ), a subset of cells which release nitric oxide (NO) in the brain and are known by its resistance in pathological conditions. Two hundred and forty NADPH-d neurons from NMDA-lesioned striatum and contralateral counterpart were tridimensionally reconstructed at 1, 3 and 7 post-lesion days (PLDs). Cell body and dendritic field areas, length of dendrites by order and fractal dimension were analyzed. There were no significant morphometric differences when NADPH-d+ neurons from lesioned and control striatal regions were compared among PLDs evaluated. Conversely, a conspicuous pallor in striatal neuropil reactivity was evidenced, especially in latter survival time. In addition, we observed a noticeable inflammatory response induced by NMDA. Our results suggest that NADPH-d+ neurons were spared from deleterious effects of acute NMDA excitotoxic damage in the striatum, reinforcing the notion that this cell group is selectively resistant to injury in the nervous system.

Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease.

Although deep brain electrical stimulation can alleviate the motor symptoms of Parkinson disease (PD), just a small fraction of patients with PD can take advantage of this procedure due to its invasive nature. A significantly less invasive method--epidural spinal cord stimulation (SCS)--has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through SCS are unknown. Here, we show that SCS reproducibly alleviates motor deficits in a primate model of PD. Simultaneous neuronal recordings from multiple structures of the cortico-basal ganglia-thalamic loop in parkinsonian monkeys revealed abnormal highly synchronized neuronal activity within each of these structures and excessive functional coupling among them. SCS disrupted this pathological circuit behavior in a manner that mimics the effects caused by pharmacological dopamine replacement therapy or deep brain stimulation. These results suggest that SCS should be considered as an additional treatment option for patients with PD.

Influence of suture on peripheral nerve regeneration and collagen production at the site of neurorrhaphy: an experimental study.

BACKGROUND: Restoration of nerve continuity and effective maintenance of coaptation are considered fundamental principles of end-to-end peripheral nerve repair. OBJECTIVE: To evaluate the influence of the number of stitches on axonal regeneration and collagen production after neurorrhaphy. METHODS: Thirty male Wistar rats were equally divided into 3 groups and were all operated on with the right sciatic nerve exposed. In 2 groups, the nerve was sectioned and repaired by means of 3 (group B) or 6 (group C) epineurium sutures with 10-0 monofilament nylon. One group (group A) was used as a control. Each animal from groups B and C underwent electrophysiological evaluation with motor action potential recordings before nerve section and again at an 8-week interval after neurorrhaphy. Nerve biopsy specimens were used for histomorphometric assessment of axonal regeneration and quantification of collagen at the repair site. RESULTS: Animals from group C had significantly lower motor action potential conduction velocities compared with control animals (P=.02), and no significant difference was seen between groups B and C. Parameters obtained from morphometric evaluation were not significantly different between these 2 groups. Type I collagen and III collagen in the epineurium were significantly higher in group C than in either the control group (P=.001 and P=.003) or group B (P=.01 and P=.02). No differences were identified for collagen I and III in the endoneurium. CONCLUSION: Using 6 sutures for nerve repair is associated with worse electrophysiological outcomes and higher amounts of type I and III collagen in the epineurium compared with control. Neurorraphy with 6 stitches is also related to a significant increase in epineurium collagen I and III compared with 3-stitch neurorraphy.

Primary hyperparathyroidism simulating motor neuron disease: case report.

We report a case of a 26-year-old man who presented a lower motor neuron syndrome due to hyperparathyroidism. Electromyography showed neurogenic features with normal nerve conduction studies. Hypercalcemia led to the discovery of a primary hyperparathyroidism with gland hyperplasia. Following parathyroid surgery there was recovery of the neurological symptoms.

Primary hyperparathyroidism simulating motor neuron disease: case report

Descrevemos o caso de homem de 26 anos que apresentou síndrome do neurônio motor inferior devido a hiperparatiroidismo. A eletromiografia mostrou aspecto neurogênico com estudos da condução normal. Hipercalcemia levou à descoberta de hiperparatiroidismo primário com hiperplasia da glândula. Após a cirurgia de ressecção da paratiróide, houve regressão dos sintomas neurológicos.