TCD assessment in fulminant hepatic failure: Improvements in cerebral autoregulation after liver transplantation.

INTRODUCTION AND OBJECTIVES: Acute liver failure, also known as fulminant hepatic failure (FHF), includes a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction and hepatic encephalopathy. The objective of this study was to assess cerebral autoregulation (CA) in 25 patients (19 female) with FHF and to follow up with seventeen of these patients before and after liver transplantation. PATIENTS AND METHODS: The mean age was 33.8 years (range 14-56, SD 13.1 years). Cerebral hemodynamics was assessed by transcranial Doppler (TCD) bilateral recordings of cerebral blood velocity (CBv) in the middle cerebral arteries (MCA). RESULTS: CA was assessed based on the static CA index (SCAI), reflecting the effects of a 20-30 mmHg increase in mean arterial blood pressure on CBv induced with norepinephrine infusion. SCAI was estimated at four time points: pretransplant and on the 1st, 2nd and 3rd posttransplant days, showing a significant difference between pre- and posttransplant SCAI (p = 0.005). SCAI peaked on the third posttransplant day (p = 0.006). Categorical analysis of SCAI showed that for most patients, CA was reestablished on the second day posttransplant (SCAI > 0.6). CONCLUSIONS: These results suggest that CA impairment pretransplant and on the 1st day posttransplant was re-established at 48-72 h after transplantation. These findings can help to improve the management of this patient group during these specific phases, thereby avoiding neurological complications, such as brain swelling and intracranial hypertension.

Perfusion tomography in early follow-up of acute traumatic subdural hematoma: a case series.

Perfusion Computed Tomography (PCT) is an alternative tool to assess cerebral hemodynamics during trauma. As acute traumatic subdural hematomas (ASH) is a severe primary injury associated with poor outcomes, the aim of this study was to evaluate the cerebral hemodynamics in this context. Five adult patients with moderate and severe traumatic brain injury (TBI) and ASH were included. All individuals were indicated for surgical evacuation. Before and after surgery, PCT was performed and cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were evaluated. These parameters were associated with the outcome at 6 months post-trauma with the extended Glasgow Outcome Scale (GOSE). Mean age of population was 46 years (SD: 8.1). Mean post-resuscitation Glasgow coma scale (GCS) was 10 (SD: 3.4). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). Preoperative CBF and MTT were 23.9 ml/100 g/min (SD: 6.1) and 7.3 s (1.3) respectively. After surgery, CBF increase to 30.7 ml/100 g/min (SD: 5.1), and MTT decrease to 5.8s (SD:1.0), however, both changes don't achieve statistically significance (p = 0.06). Additionally, CBV increase after surgery, from 2.34 (SD: 0.67) to 2.63 ml/100 g (SD: 1.10), (p = 0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome at 6 months was 0.94 (p = 0.054). One patient died with the highest preoperative MTT (9.97 s) and CBV (4.51 ml/100 g). CBF seems to increase after surgery, especially when evaluated together with the MTT values. It is suggested that the improvement in postoperative brain hemodynamics correlates to favorable outcome.

Contribution of intracranial pressure to human dynamic cerebral autoregulation after acute brain injury.

Cerebral perfusion pressure (CPP) is normally expressed by the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP) but comparison of the separate contributions of MAP and ICP to human cerebral blood flow autoregulation has not been reported. In patients with acute brain injury (ABI), internal jugular vein compression (IJVC) was performed for 60 s. Dynamic cerebral autoregulation (dCA) was assessed in recordings of middle cerebral artery blood velocity (MCAv, transcranial Doppler), and invasive measurements of MAP and ICP. Patients were separated according to injury severity as having whole/undamaged skull, large fractures, or craniotomies, or following decompressive craniectomy. Glasgow coma score was not different for the three groups. IJVC induced changes in MCAv, MAP, ICP, and CPP in all three groups. The MCAv response to step changes in MAP and ICP expressed the dCA response to these two inputs and was quantified with the autoregulation index (ARI). In 85 patients, ARI was lower for the ICP input as compared with the MAP input (2.25 ± 2.46 vs. 3.39 ± 2.28; P < 0.0001), and particularly depressed in the decompressive craniectomy (DC) group (n = 24, 0.35 ± 0.62 vs. 2.21 ± 1.96; P < 0.0005). In patients with ABI, the dCA response to changes in ICP is less efficient than corresponding responses to MAP changes. These results should be taken into consideration in studies aimed to optimize dCA by manipulation of CPP in neurocritical patients.

Critical Closing Pressure and Cerebrovascular Resistance Responses to Intracranial Pressure Variations in Neurocritical Patients.

BACKGROUND: Critical closing pressure (CrCP) and resistance-area product (RAP) have been conceived as compasses to optimize cerebral perfusion pressure (CPP) and monitor cerebrovascular resistance, respectively. However, for patients with acute brain injury (ABI), the impact of intracranial pressure (ICP) variability on these variables is poorly understood. The present study evaluates the effects of a controlled ICP variation on CrCP and RAP among patients with ABI. METHODS: Consecutive neurocritical patients with ICP monitoring were included along with transcranial Doppler and invasive arterial blood pressure monitoring. Internal jugular veins compression was performed for 60 s for the elevation of intracranial blood volume and ICP. Patients were separated in groups according to previous intracranial hypertension severity, with either no skull opening (Sk1), neurosurgical mass lesions evacuation, or decompressive craniectomy (DC) (patients with DC [Sk3]). RESULTS: Among 98 included patients, the correlation between change (Δ) in ICP and the corresponding ΔCrCP was strong (group Sk1 r = 0.643 [p = 0.0007], group with neurosurgical mass lesions evacuation r = 0.732 [p < 0.0001], and group Sk3 r = 0.580 [p = 0.003], respectively). Patients from group Sk3 presented a significantly higher ΔRAP (p = 0.005); however, for this group, a higher response in mean arterial pressure (change in mean arterial pressure p = 0.034) was observed. Exclusively, group Sk1 disclosed reduction in ICP before internal jugular veins compression withholding. CONCLUSIONS: This study elucidates that CrCP reliably changes in accordance with ICP, being useful to indicate ideal CPP in neurocritical settings. In the early days after DC, cerebrovascular resistance seems to remain elevated, despite exacerbated arterial blood pressure responses in efforts to maintain CPP stable. Patients with ABI with no need of surgical procedures appear to remain with more effective ICP compensatory mechanisms when compared with those who underwent neurosurgical interventions.

Improvement in neurological outcome and brain hemodynamics after late cranioplasty.

BACKGROUND: Early cranioplasty has been encouraged after decompressive craniectomy (DC), aiming to reduce consequences of atmospheric pressure over the opened skull. However, this practice may not be often available in low-middle-income countries (LMICs). We evaluated clinical improvement, hemodynamic changes in each hemisphere, and the hemodynamic balance between hemispheres after late cranioplasty in a LMIC, as the institution's routine resources allowed. METHODS: Prospective cohort study included patients with bone defects after DC evaluated with perfusion tomography (PCT) and transcranial Doppler (TCD) and performed neurological examinations with prognostic scales (mRS, MMSE, and Barthel Index) before and 6 months after surgery. RESULTS: A final sample of 26 patients was analyzed. Satisfactory improvement of neurological outcome was observed, as well as significant improvement in the mRS (p = 0.005), MMSE (p < 0.001), and Barthel Index (p = 0.002). Outpatient waiting time for cranioplasty was 15.23 (SD 17.66) months. PCT showed a significant decrease in the mean transit time (MTT) and cerebral blood volume (CBV) only on the operated side. Although most previous studies have shown an increase in cerebral blood flow (CBF), we noticed a slight and nonsignificant decrease, despite a significant increase in the middle cerebral artery flow velocity in both hemispheres on TCD. There was a moderate correlation between the MTT and contralateral muscle strength (r = - 0.4; p = 0.034), as well as between TCD and neurological outcomes ipsilateral (MMSE; r = 0.54, p = 0.03) and contralateral (MRS; p = 0.031, r = - 0.48) to the operated side. CONCLUSION: Even 1 year after DC, cranioplasty may improve cerebral perfusion and neurological outcomes and should be encouraged.

Dual origin of vertebral artery and intimal relationship with spontaneous artery dissection: a case report and systematic review.

Dual origin of the vertebral artery (VA) is an uncommon anatomical variation. We describe a case of duplication origin at right vertebral artery (RVA) found incidentally in one elderly patient on investigation for cerebral aneurysm. Angiogram study showed a pseudoaneurysm at V4 segment of the RVA associated with embryological anatomy. The authors performed a systematic review of the similar cases reported worldwide.

Efficacy and adverse event profile of cannabidiol and medicinal cannabis for treatment-resistant epilepsy: Systematic review and meta-analysis.

This paper aimed to systematically examine the efficacy and adverse event (AE) profile of cannabidiol and medicinal cannabis by analyzing qualitative and meta-analytic data. We used the terms ("Cannabidiol" OR "Cannabis") AND "Epilepsy" AND ("Treatment" OR "Therapeutics") as keywords to retrieve studies indexed on PubMed, ScienceDirect, and CENTRAL databases. The inclusion criteria were as follows: clinical studies with a longitudinal observational design and intervention using cannabinoid derivatives, especially cannabidiol and medicinal cannabis, whereby some results involved the frequency of epileptic seizures. We used Cochrane Collaboration's Review Manager software (RevMan 5.1.6) for the meta-analysis and dichotomized the articles to a confidence interval of 95%. From 236 articles, we selected 16 for descriptive analysis; we selected only 4 for the meta-analysis. According to the results, a statistically meaningful effect of cannabidiol compared with placebo was observed (p < 0.00001). When comparing treatment with cannabidiol or medicinal cannabis, significance was not found for the AE profile (p = 0.74). As AEs for cannabidiol were more common under short-term than under long-term treatment (p < 0.00001), this approach was favorable in the long term. Furthermore, cannabidiol is more effective than placebo, regardless of the etiology of epileptic syndromes and dosage. Overall, the AE profile did not differ across treatments with cannabidiol or medicinal cannabis, though it did differ favorably for long-term than for short-term treatment.

The influence of intracranial hypertension on static cerebral autoregulation.

OBJECTIVES: To analyze the influences of mild and severe intracranial hypertension on cerebral autoregulation (CA). PATIENTS AND METHODS: Duroc piglets were monitored with an intracranial pressure (ICP) catheter. Intracranial hypertension was induced via infusion of 4 or 7 ml of saline solution by a bladder catheter that was inserted into the parietal lobe. The static cerebral autoregulation (sCA) index was evaluated via cerebral blood flow velocities (CBFv). Piglets with ICPs ≤ 25 and > 25 mmHg were considered as group 1 and 2, respectively. Continuous variables were evaluated using the Kolmogorov-Smirnov goodness-of-fit test. The main parameters were collected before and after ICH induction and compared using two-factor mixed-design ANOVAs with the factor of experimental group (mild and severe ICH). RESULTS: In group 1 (ICP ≤ 25 mmHg), there were significant differences in sCA (p = .01) and ICP (p = .0002) between the basal and balloon inflation conditions. In group 2 (ICP > 25 mmHg), there were significant differences in CBFv (p = .0072), the sCA index (p = .0001) and ICP (p = .00001) between the basal and balloon inflation conditions. CONCLUSION: We conclude that intracranial hypertension may have a direct effect on sCA.

Inducing Brain Cooling Without Core Temperature Reduction in Pigs Using a Novel Nasopharyngeal Method: An Effectiveness and Safety Study.

BACKGROUND: Acute brain lesions constitute an alarming public health concern. Neuroprotective therapies have been implemented to stabilize, prevent, or reduce brain lesions, thus improving neurological outcomes and survival rates. Hypothermia is the most effective approach, mainly attributed to the reduction in cellular metabolic activity. Whole-body cooling is currently implemented by healthcare professionals; however, adverse events are frequent, limiting the potential benefits of therapeutic hypothermia. Therefore, selective methods have been developed to reduce adverse events while delivering neuroprotection. Nasopharyngeal approaches are the safest and most effective methods currently considered. Our primary objective was to determine the effects of a novel nasopharyngeal catheter on the brain temperature of pigs. METHODS: In this prospective, non-randomized, interventional experimental trial, 10 crossbred pigs underwent nasopharyngeal cooling for 60 min followed by 15 min of rewarming. Nasopharyngeal catheters were inserted into the left nostril and properly positioned at the nasopharyngeal cavity. RESULTS: Nasopharyngeal cooling was associated with a decrease in brain temperature, which was more significant in the left cerebral hemisphere (p = 0.01). There was a reduction of 1.47 ± 0.86 °C in the first 5 min (p < 0.001), 2.45 ± 1.03 °C within 10 min (p < 0.001), and 4.45 ± 1.36 °C after 1 h (p < 0.001). The brain-core gradient was 4.57 ± 0.87 °C (p < 0.001). Rectal, esophageal, and pulmonary artery temperatures and brain and systemic hemodynamic parameters, remained stable during the procedure. Following brain cooling, values of oxygen partial pressure in brain tissue significantly decreased. No mucosal lesions were detected during nasal, pharyngeal, or oral inspection after nasopharyngeal catheter removal. CONCLUSIONS: In this study, a novel nasopharyngeal cooling catheter effectively induced and maintained exclusive brain cooling when combined with effective counter-warming methods. Exclusive brain cooling was safe with no device-related local or systemic complications and may be desired in selected patient populations.

Latin American Consensus Statement for the Use of Contrast-Enhanced Transcranial Ultrasound as a Diagnostic Test for Detection of Right-to-Left Shunt.

BACKGROUND: The role of patent foramen ovale is a field of debate and current publications have increasing controversies about the patients' management in young undetermined stroke. Work up with echocardiography and transcranial Doppler (TCD) can aid the decision with better anatomical and functional characterization of right-to-left shunt (RLS). Medical and interventional strategy may benefit from this information. SUMMARY: a group of experts from the Latin American participants of the Neurosonology Research Group (NSRG) of World Federation of Neurology created a task force to review literature and describe the better methodology of contrast TCD (c-TCD). All signatories of the present consensus statement have published at least one study on TCD as an author or co-author in an indexed journal. Two meetings were held while the consensus statement was being drafted, during which controversial issues were discussed and voted on by the statement signatories. The statement paper was reviewed and approved by the Executive Committee of the NSRG of the World Federation of Neurology. The main objective of this consensus statement is to establish a standardization of the c-TCD technique and its interpretation, in order to improve the informative quality of the method, resulting in expanding the application of TCD in the clinical setting. These recommendations optimize the comparison of different diagnostic methods and encourage the use of c-TCD for RLS screening and complementary diagnosis in multicenter studies.

Pulmonary paracoccidioidomycosis associated with the use of natalizumab in multiple sclerosis.

BACKGROUND: Natalizumab (NTZ) is a monoclonal antibody with an immunosuppressive effect that reduces the inflammation of the central nervous system, and it has been used for the treatment of relapsing-remitting multiple sclerosis (RRMS). In patients with low cellular immune response, systemic mycosis arising from endemic areas may occur. RESULTS AND CONCLUSION: In this article, we will describe a case of paracoccidioidomycosis as a complication to treatment with NTZ in an RRMS patient.

Pooling data from different populations: should there be regional differences in cerebral haemodynamics?

BACKGROUND: Though genetic and environmental determinants of systemic haemodynamic have been reported, surprisingly little is known about their influences on cerebral haemodynamics. We assessed the potential geographical effect on cerebral haemodynamics by comparing the individual differences in cerebral blood flow velocity (CBFv), vasomotor tone (critical closing pressure- CrCP), vascular bed resistance (resistance-area product- RAP) and cerebral autoregulation (CA) mechanism on healthy subjects and acute ischaemic stroke (AIS) patients from two countries. METHODS: Participants were pooled from databases in Leicester, United Kingdom (LEI) and São Paulo, Brazil (SP) research centres. Stroke patients admitted within 48 h of ischaemic stroke onset, as well as age- and sex-matched controls were enrolled. Beat-to-beat blood pressure (BP) and bilateral mean CBFv were recorded during 5 min baseline. CrCP and RAP were calculated. CA was quantified using transfer function analysis (TFA) of spontaneous oscillations in arterial BP and mean CBFv, and the derived autoregulatory index (ARI). RESULTS: A total of 100 participants (50 LEI and 50 SP) were recruited. No geographical differences were found. Both LEI and SP AIS participants showed lower values of CA compared to controls. Moreover, the affected hemisphere presented lower resting CBFv and higher RAP compared to the unaffected hemisphere in both populations. CONCLUSIONS: Impairments of cerebral haemodynamics, demonstrated by several key parameters, was observed following AIS compared to controls irrespective of geographical region. These initial results should encourage further research on cerebral haemodynamic research with larger cohorts combining different populations.

Relationship between endothelial nitric oxide synthase (eNOS) and natural history of intracranial aneurysms: meta-analysis.

The aneurysmal subarachnoid hemorrhage is a major public health problem described as a sudden drastic event with no warning symptoms and high morbidity and mortality rates. The role of the endothelial isoform of nitric oxide synthase gene polymorphism in intracranial aneurysms (IAs) is still a matter of controversy with divergent findings among European, American, and Asian populations. Our study purposed to test the association between intracranial aneurysms formation and nitric oxide gene polymorphisms through a systematic review and meta-analysis. Systematic search on Medline, Lilacs, and EMBASE was performed. The primary search resulted in 139 papers, out of which 9 met our inclusion criteria after a full text analysis. The dominant T786C model found a significant association with IA (OR 1.22, 95 % CI 1.04-1.44, p = 0.01), so did studies of the recessive T786C model (OR 0.37, 95 % CI 0.30-0.45, p < 0.0001) but with opposite effect. Our findings support the presence of the T786C polymorphism as a predictor for the development of intracranial aneurysm in the cerebral vascular system. More studies are necessary in order to elucidate the pathways of the endothelial nitric oxide synthase (eNOS) in cerebrovascular diseases and in defining how different allelic combinations of the eNOS gene single-nucleotide polymorphism (SNP) could favor this pathological process.

Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson's disease: A diagnostic performance study and meta-analysis.

OBJECTIVES: Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy. METHODS: Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures. RESULTS: In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I2 = 91.9 %). CONCLUSIONS: SN-FA cannot be used as an isolated measure to diagnose PD. KEY POINTS: • SN-FA appears insufficiently sensitive and specific to diagnose PD. • Radiologists must be careful when translating mean group results to clinical practice. • Imaging protocol and analysis standardization is necessary for developing reproducible quantitative biomarkers.

Modified Pfeffer Questionnaire for Functional Assessment in Parkinson Disease.

INTRODUCTION: It was proposed to modify the Pfeffer questionnaire (PQ) for functional assessment in patients with Parkinson disease (PD). AIM: To determine the cutoff score for diagnosis of functional impairment in patients with PD by modified PQ (mPQ). METHODS: A total of 110 patients with PD were enrolled into the study, and a neuropsychological test battery was performed to assess their cognitive status. Regarding functional assessment, the mPQ has been applied, and their results were compared to the functional assessment by Informant Questionnaire on Cognitive Decline in the Elderly adapted for use in Brazil (IQCODE-BR). The statistical analysis was accomplished through receiver operating characteristic (ROC) curve with evaluation of the area under the curve, sensitivity, and specificity of the new cutoff point. RESULTS: Eighty-nine patients with PD were evaluated with a mean age of 63.69 ± 9.14 years. Cognitive status categorization was 28.10% as normal, 44.94% as mild cognitive impairment, and 26.96% of patients as dementia associated with PD. The average score on PQ was 3.49 ± 4.79 and on the mPQ 2.56 ± 3.49. In IQCODE-BR, the average score was 6.75 ± 32.72. The ROC curve for the new cutoff point presented 47.4% sensitivity, 88.10% specificity, and 0.757 of area under the curve, with a standard deviation of 0.055 (95% confidence interval: 0.650-0.864). CONCLUSION: 3.5 is proposed as the cutoff point to define functional impairment in patients with PD by mPQ.

Cerebral hemodynamics in sepsis assessed by transcranial Doppler: a systematic review and meta-analysis.

Cerebral microcirculation is gradually compromised during sepsis, with significant reductions in the function of capillaries and blood perfusion in small vessels. Transcranial Doppler ultrasound (TCD) has been used to assess cerebral circulation in a typical clinical setting. This study was to systematically review TCD studies, assess their methodological quality, and identify trends that can be associated with the temporal evolution of sepsis and its clinical outcome. A meta-analysis of systematic reviews was conducted according to the PRISMA statement. Articles were searched from 1982 until the conclusion of this review in December 2015. Twelve prospective and observational studies were selected. Evaluations of cerebral blood flow, cerebral autoregulation, and carbon dioxide (CO2) vasoreactivity were summarized. A temporal pattern of the evolution of the illness was found. In early sepsis, the median blood flow velocity (Vm) and pulsatility index (PI) increased, and the cerebral autoregulation (CA) remained unchanged. In contrast, Vm normalization, PI reduction and CA impairment were found in later sepsis (patients with severe sepsis or septic shock). Cerebral haemodynamic is impaired in sepsis. Modifications in cerebral blood flow may be consequence to the endothelial dysfunction of the microvasculature induced by the release of inflammatory mediators. A better understanding of cerebral hemodynamics may improve the clinical management of patients with sepsis and, consequently, improve clinical outcomes.

Puerperal Extracranial Vertebral Artery Dissection and Nonaneurysmal Subarachnoid Hemorrhage.

Previously reported only a few times before, we present a case of extracranial vertebral dissection and spontaneous frontoparietal subarachnoid hemorrhage (SAH) in the puerperium, discussing possible mechanisms and difficulties in management. A 35-year-old woman presented 10 days postcaesarean section with neck pain and vertigo with normal initial investigations. Following recurrent vertigo, headache, and ataxia, imaging revealed a frontoparietal SAH and vertebral artery dissection. The patient was consequently treated with aspirin, and then following a return of symptoms 3 weeks later, warfarin therapy was continued for 6 months. The possible underlying mechanisms for this case are discussed, including reversible cervical vasoconstriction syndrome and posterior reversible encephalopathy syndrome, although neither was identified. The small SAH alongside recurrent posterior circulation symptoms resulted in the initiation of antithrombotic therapy. This report supports studies demonstrating higher incidence of cervicocephalic arterial dissection in the puerperium. Moreover, the heterogeneous presentation and manifestations of such cases require individualized treatment, and warrant studies into underlying mechanisms behind extracranial dissection and nonaneurysmal SAH.

Role of computed tomography angiography and perfusion tomography in diagnosing brain death: A systematic review.

BACKGROUND: Several complications make the diagnosis of brain death (BD) medically challenging and a complimentary method is needed for confirmation. In this context, computed tomography angiography (CTA) and computed tomography perfusion (CTP) could represent valuable alternatives; however, the reliability of CTA and CTP for confirming brain circulatory arrest remains unclear. METHODS: A systematic review was performed to identify relevant studies regarding the use of CTA and CTP as ancillary tests for BD confirmation. RESULTS: Three hundred twenty-two patients were eligible for the meta-analysis, which exhibited 87.5% sensitivity. CTA image evaluation protocol exhibited variations between medical institutions regarding which intracranial vessels should be considered to determine positive or negative test results. CONCLUSIONS: For patients who were previously diagnosed with BD according to clinical criteria, CTA demonstrated high sensitivity to provide radiologic confirmation. The current evidence that supports the use of CTA in BD diagnosis is comparable to other methods applied worldwide.

Milestones in Friedreich ataxia: more than a century and still learning.

Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia worldwide. This review highlights the main clinical features, pathophysiological mechanisms, and therapeutic approaches for FRDA patients. The disease is characterized by a combination of neurological involvement (ataxia and neuropathy), cardiomyopathy, skeletal abnormalities, and glucose metabolism disturbances. FRDA is caused by expanded guanine-adenine-adenine (GAA) triplet repeats in the first intron of the frataxin gene (FXN), resulting in reduction of messenger RNA and protein levels of frataxin in different tissues. The molecular and metabolic disturbances, including iron accumulation, lead to pathological changes characterized by spinal cord and dorsal root ganglia atrophy, dentate nucleus atrophy without global cerebellar volume reduction, and hypertrophic cardiomyopathy. DNA analysis is the hallmark for the diagnosis of FRDA. There is no specific treatment to stop the disease progression in FRDA patients. However, a number of drugs are under investigation. Therapeutic approaches intend to improve mitochondrial functioning and to increase FXN expression.

Comparing methods for determining motor-hand lateralization based on fTCD signals.

The lateralization index (LI) as determined from functional transcranial Doppler sonography (fTCD) can be used to determine the hemispheric organization of neural activation during a behavioral task. Previous studies have proposed different methods to determine this index, but to our knowledge no studies have compared the performance of these methods. In this study, we compare two established methods with a simpler method proposed here. The aim was to see whether similar results could be achieved with a simpler method and to give an indication of the analysis steps required to determine the LI. A simple unimanual motor task was performed while fTCD was acquired, and the LI determined by each of these methods was compared. In addition, LI determined by each method was related to behavioural output in the form of degree of handedness. The results suggest that although the methods differed in complexity, they yielded similar results when determining the lateralization of motor functions, and its correlation with behavior. Further investigation is needed to expand the conclusions of this preliminary study, however the new method proposed in the paper has great potential as it is much simpler than the more established methods yet yields similar results.