PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells.

Longstanding effects of continuous theta burst stimulation in adult amblyopes.

CLINICAL RELEVANCE: Continuous theta burst stimulation may be an important tool in the therapeutic management of amblyopia, when trying to correct the established neuronal imbalance. It is important to understand whether two sessions of continuous theta burst stimulation produce greater and longstanding changes in visual acuity and suppressive imbalance than one session of continuous theta burst stimulation. BACKGROUND: We hypothesise that through the usage of continuous theta burst stimulation (cTBS) it is possible to change cortical excitability in a situation where visual impairment is present. METHODS: We selected 22 adult amblyopes, 18 females and 4 males, with an age range of 20-59 years. They were randomised into two groups: group A with 10 amblyopes was submitted to one session of cTBS and group B with 12 amblyopes submitted to two sessions of cTBS. Visual acuity (VA) and suppressive imbalance (SI) were evaluated immediately before and after stimulation in both groups A and B. A follow-up was done in both groups. RESULTS: For both group A and B, the VA improvements were significant after cTBS (p = 0.005 and p = 0.003, respectively). Regarding SI, both group A and B had significant improvements after cTBS (p = 0.03 and p = 0.005, respectively). Comparing groups, A and B no significant differences were found with regard to the results obtained both for VA (p = 0.72) and SI (p = 0.24). However, significant differences were found between group A and B with regard to the duration of stimulation effect for VA (p = 0.049) and SI (p = 0.03). CONCLUSION: We conclude that two sessions of cTBS do not produce better results than one session of stimulation. However, it seems that two sessions of cTBS produce longstanding effects in VA and SI.

Can pattern electroretinography be a relevant diagnostic aid in amblyopia? - A systematic review.

INTRODUCTION: Pattern Electroretinography (PERG) is a highly sensitive electrophysiological technique used as an indicator of changes in retinal macular area. Amblyopia seems to result from a cortical visual imbalance but changes at the retinal level may also be present. The purpose of this systematic review was to evaluate if there are any consistent changes described in the scientific literature in PERG responses of amblyopic eyes. MATERIALS AND METHODS: Searches were conducted in PubMed and Embase databases, using the keywords "Electroretinography" and "Amblyopia", combined with MeSH or Emtree terms "Pattern Electroretinography", "amblyopia", "PERG" and "amblyopia". PERG P50-N95 amplitude and P50 latency were analysed as well as the methodology used. RESULTS: A total of 234 articles were found and 6 articles were included for review. One of the articles reported results in adults and five of them in children. One of the articles in children reported no changes in either P50-N95 amplitude or P50 latency. All articles that described differences between the amblyopic eye and the normal eye found a decrease in P50-N95 amplitude and/or a delay in P50 latency. CONCLUSIONS: This review shows promising findings for the use of PERG in amblyopia as an aid in the diagnostic protocol, since this technique may be able to detect an apparent functional impairment of the amblyopic eye.

Theta burst stimulation over the prefrontal cortex: Effects on cerebral oximetry and cardiovascular measures in healthy humans.

Theta Burst Stimulation (TBS) is a non-invasive neurophysiological technique, able to induce changes in synaptic activity. Research suggests that TBS may induce changes in cerebral oxygenation, cerebral blood flow, blood pressure and heart rate but there are conflicting results across studies. Thus, the objective of our sham-controlled study is to evaluate if TBS applied to the dorsolateral prefrontal cortex (DLPFC) of healthy volunteers produces changes in cerebral oximetry, heart rate and blood pressure. Forty-nine volunteers of both sexes were randomly allocated to one of five stimulation groups. Before and after real TBS or sham stimulation, blood pressure, heart rate, and cerebral oxygenation of the volunteers were measured. Cerebral oxygenation values were obtained with a near infra-red spectroscopy system. We found a significant reduction in left cortex oximetry after continuous TBS (cTBS) over the left DLPFC (p = 0.039) and a non-significant reduction in right cortex oximetry (p = 0.052). Right hemisphere inhibition (using cTBS) seemed to originate a significant reduction of 8 mmHg in systolic arterial pressure. No other changes were seen in oximetry, cardiac frequency and diastolic arterial pressure. In our group of normal subjects, cTBS applied to the left DLPFC was able to reduce oxygenation in the left cortex. Right hemisphere inhibition was associated with a significant reduction in systolic pressure.

Can theta burst stimulation safely influence auditory hearing thresholds in healthy young adults?

OBJECTIVE: This TBS sham-controlled study aimed to evaluate the effects of intermittent TBS (iTBS) and continuous TBS (cTBS) upon ipsilateral hearing thresholds after stimulation on the left auditory cortex. METHODS: Sixty healthy adults, aged between 19 and 32 years (median of 23 years), were randomly distributed into three groups and underwent iTBS, cTBS or sham stimulation. Each double-blind experimental session comprised two pure tone audiometric evaluations per subject, before and after stimulation. To assess volunteer safety, a follow-up of at least 48 hours was implemented. RESULTS: The iTBS group mean thresholds displayed a tendency to decrease after stimulation, predominantly in the 500 Hz-6000 Hz interval and group comparisons revealed significant differences between the iTBS and sham groups for 500 Hz (p = 0.041) and between the iTBS and cTBS groups for 4000 Hz (p = 0.038). Neither relevant side effects nor any significant hearing threshold impairment after active or sham stimulation were found. CONCLUSIONS: A single stimulation session led to an effective neuromodulation of the auditory cortex, reflected in lower thresholds when using iTBS. SIGNIFICANCE: These encouraging results with this safe noninvasive tool suggest that iTBS may have the potential to positively influence hearing thresholds.