Impaired cerebral autoregulation in Fabry disease: A case-control study.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is a common manifestation among patients with Fabry disease (FD). As a biomarker of cerebral small vessel disease, the prevalence of impaired cerebral autoregulation as assessed by transcranial Doppler (TCD) ultrasonography was evaluated in FD patients and healthy controls. METHODS: TCD was performed to assess pulsatility index (PI) and vasomotor reactivity expressed by breath-holding index (BHI) for the middle cerebral arteries of included FD patients and healthy controls. Prevalence of increased PI (>1.2) and decreased BHI (<0.69) and ultrasound indices of cerebral autoregulation were compared in FD patients and controls. The potential association of ultrasound indices of impaired cerebral autoregulation with white matter lesions and leukoencephalopathy on brain MRI in FD patients was also evaluated. RESULTS: Demographics and vascular risk factors were similar in 23 FD patients (43% women, mean age: 51 ± 13 years) and 46 healthy controls (43% women, mean age: 51 ± 13 years). The prevalence of increased PI (39%; 95% confidence interval [CI]: 20%-61%), decreased BHI (39%; 95% CI: 20%-61%), and the combination of increased PI and/or decreased BHI (61%; 95% CI: 39%-80%) was significantly (p < .001) higher in FD patients compared to healthy controls (2% [95% CI: 0.1%-12%], 2% [95% CI: 0.1%-12%], and 4% [95% CI: 0.1%-15%], respectively). However, indices of abnormal cerebral autoregulation were not associated independently with white matter hyperintensities and presented a low-to-moderate predictive ability for the discrimination of FD patients with and without white matter hyperintensities. CONCLUSIONS: Impaired cerebral autoregulation as assessed by TCD appears to be highly more prevalent among FD patients compared to healthy controls.

Non-pharmacological Interventions on Pain and Quality of Life in Chemotherapy Induced Polyneuropathy: Systematic Review and Meta-Analysis.

BACKGROUND/AIM: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment, resulting in pain, numbness, instability, and thus affecting quality of life (QoL), occasionally leading to discontinuation of chemotherapy. Pharmacological treatments are not sufficient. Non-pharmacological interventions (NPIs) have also been tried. This study aimed to systematically review the efficacy of NPIs on pain and QoL in patients suffering from CIPN. MATERIALS AND METHODS: The databases searched were Pubmed, Cohrane, and Scopus for randomized controlled trials (RCTs) published in the last 5 years (2017-2022). Studies were considered eligible, if they assessed adult patients suffering from CIPN because of any chemotherapeutic drug for any type and any stage of cancer and if study protocols included non-pharmacological intervention with a structured protocol. RESULTS: A total of 1,496 records were identified. Finally, 10 RCTs including 495 patients (253 in the intervention group and 242 in the control group) were included for meta-analysis. Intervention protocols included acupuncture (n=6), exercise (n=3), and yoga (n=1). NPIs significantly reduced neuropathic pain. However, the effect on QoL was not significant. CONCLUSION: NPIs are beneficial in the treatment of pain in patients with CIPN but their impact on QoL is not statistically supported. Larger sample sizes, more homogenous in outcome measures and interventions are needed to further explore NPIs' efficacy on CIPN symptoms.

Neurophysiological and ultrasonographic comparative study of autonomous nervous system in patients suffering from fibromyalgia and generalized anxiety disorder.

BACKGROUND: Fibromyalgia (FM) and generalized anxiety disorder (GAD) share common clinical features: they both affect women more than men, their diagnosis is based solely on clinical criteria, and some of the symptoms such as anxiety, aches and muscle tension, sleep disorders, and cognitive dysfunction occur in both diseases. For both conditions, an underlying dysregulation of the autonomic nervous system (ANS) has been proposed. OBJECTIVE: The aims of this study were to investigate ANS dysfunction in FM and GAD and compare them with controls. METHODS: Sympathetic skin response (SSR) from palm and sole and cross-sectional area (CSA) of bilateral vagus nerves (VN) were measured in 28 healthy controls, 21 FM patients, and 24 GAD patients. RESULTS: CSA of VN was significantly smaller in FM patients (right: 1.97 ± 0.74mm2, left: 1.75 ± 0.65 mm2) and GAD patients (right: 2.12 ± 0.97mm2, left: 1.71 ± 0.86 mm2) compared to controls (right: 3.21 ± 0.75 mm2, left: 2.65 ± 1.13 mm2, p < 0.001, but did not differ between the two patient groups. SSR parameters were similar between patients and controls. SSR latency correlated to clinical scales (FM Widespread Pain Index) in the FM group (r = 0.515, p = 0.02 and r = 0.447, p = 0.05) for the upper and lower limbs respectively, but no other correlation between clinical and neurophysiological parameters was identified. CONCLUSION: This study confirms similar ANS abnormalities in FM and GAD that fairly distinguish them from controls and support the hypothesis of a common pathophysiological substrate underlying both conditions.

Three new case reports of Arteriovenous malformation-related Amyotrophic Lateral Sclerosis.

Despite recent advances in genetics, in most cases of Amyotrophic Lateral Sclerosis (ALS) no etiological factor can be identified. Cerebral Arteriovenous Malformations (AVMs) have been associated with ALS development in a few studies, but the nature of this connection is unclear. We report here 3 additional cases of young adults, who had undergone repeated embolizations for complex AVMs, and who then developed, after many years, ALS symptoms and signs. In two of these cases Vascular Endothelial Growth Factor (VEGF) levels were found to be extremely high, in contrast to previous reports. Our 3 cases, together with the previously reported ones, suggest that a subgroup of patients with AVMs, with a particular profile of a complex nidus with repeated embolization procedures, are at increased risk of developing ALS. The reason for this association is unclear, but may relate to dysregulation of secreted vascular factors, as suggested by our VEGF results, or more broadly to the neurovascular hypothesis of ALS. Alternatively, a transneuronal type of neurodegeneration may be involved.

Endogenous adenosine induces NMDA receptor-independent persistent epileptiform discharges in dorsal and ventral hippocampus via activation of A2 receptors.

Although adenosine is widely assumed to be an endogenous anticonvulsant its role in epileptogenesis is still contradictory. Using slices from the dorsal (DH) and the vental (VH) rat hippocampus and extracellular recordings from the CA3 field we aimed to determine the effects of endogenous adenosine on the expression and long-term maintenance of epileptiform activity induced by blockade of adenosine receptors types A(1) (A(1)R) and A(2) (A(2)R) under conditions of low magnesium. We found that the A(1)Rs blockade induced persistent epileptiform discharges (PED) more frequently in VH (by 52%) than in DH (by 31%). The induction of PED upon an additional blockade of A(2)Rs increased in VH (by 48%) but decreased in DH (by 74%). Remarkably, the increment in VH was prevented by a blockade of NMDARs. A blockade of A(2)Rs increased the NMDAR-mediated component of evoked synaptic potential in both VH and DH (by ~100%) but suppressed the non-NMDAR-mediated component in DH but not VH. A blockade of A(1)Rs induced PED equally in DH (76%) and VH (80%) via a NMDAR-independent mechanism. A blockade of A(2)Rs under blockade of A(1)Rs and NMDARs reduced the PED to 17% in DH and to 38% in VH. These findings show that A(2)Rs play a different role in the long-term maintenance of epileptiform activity between DH and VH and suggest that endogenous activation of A(2)Rs facilitates NMDAR-independent induction of PED in both hippocampal poles, but suppresses NMDAR-dependent induction of PED in VH.