Two rare autosomal recessive neurological disorders identified by combined genetic approaches in a single consanguineous family with multiple offspring.

INTRODUCTION: Neurodevelopmental disorders (NDDs) refer to a broad range of diseases including developmental delay, intellectual disability, epilepsy, autism spectrum disorders, and attention-deficit/hyperactivity disorder caused by dysfunctions in tightly controlled brain development. The genetic backgrounds of NDDs are quite heterogeneous; to date, recessive or dominant variations in numerous genes have been implicated. Herein, we present a large consanguineous family from Turkiye, who has been suffering from NDDs with two distinct clinical presentations. METHODS AND RESULTS: Combined in-depth genetic approaches led us to identify a homozygous frameshift variant in NALCN related to NDD and expansion of dodecamer repeat in CSTB related to Unverricht-Lundborg disease (ULD). Additionally, we sought to functionally analyze the NALCN variant in terms of mRNA expression level and current alteration. We have both detected a decrease in the level of premature stop codon-bearing mRNA possibly through nonsense-mediated mRNA decay mechanism and also an increased current in patch-clamp recordings for the expressed truncated protein. CONCLUSION: In conclusion, increased consanguinity may lead to the revealing of distinct rare neurogenetic diseases in a single family. Exome sequencing is generally considered the first-tier diagnostic test in individuals with NDD. Yet we underline the fact that customized approaches other than exome sequencing may be used as in the case of ULD to aid diagnosis and better genetic counseling.

Acute effect of sphenopalatine ganglion block with lidocaine in a patient with SUNCT.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing/short-lasting unilateral neuralgiform headache with cranial autonomic features (SUNCT/SUNA) is a rare severe headache. At the time of an attack, it can hinder a patient from eating and requires acute intervention. The sphenopalatine ganglion is an extracranial parasympathetic ganglion with both sensory and autonomic fibers. Sphenopalatine ganglion block has long been used in the treatment of headache, particularly when conventional methods have failed. Here, we present a patient who was resistant to intravenous lidocaine, but responded rapidly to sphenopalatine ganglion block during an acute episode of SUNCT/SUNA.

The relationship among neutrophil to lymphocyte ratio, stroke territory, and 3-month mortality in patients with acute ischemic stroke.

BACKGROUND: Stroke therapy options have focused on limiting the infarct volume. Neutrophil to lymphocyte ratio (NLR) can be valuable to detect the patients that required intensive treatment at early stage by predicting infarct volume. The aim of this study is to evaluate the relationship between NLR and infarct volume according to the stroke territory, and to determine the prognostic value of NLR for predicting 3-month mortality in acute ischemic stroke (AIS) patients. METHODS: A total of 107 patients with AIS were enrolled and followed up 3 months in terms of mortality. Study population was divided into two groups according to the stroke territory: anterior circulating stroke (ACS) and posterior circulating stroke (PCS). All patients underwent magnetic resonance imaging. The complete blood count and venous blood samples were obtained from the patients on admission to the emergency department. RESULTS: There were no difference between ACS and PCS groups regarding baseline characteristics and co-morbid diseases. Also, C-reactive protein and NLR were similar between two groups. In correlation analyses, infarct volume was significantly correlated with CRP and NLR in ACS (r = 0.350, p = 0.001 and r = 0.482, p ≤ 0.001, respectively), but not correlated with infarct volume in PCS. Also, NLR was correlated with NIHHS in only ACS group (r = 0.326, p = 0.002). Multivariate analysis showed that NLR was the only independent predictor of 3-month mortality (OR 1.186, 95% CI 1.032-1.363, p = 0.016). CONCLUSION: NLR is significantly correlated with ACS infarct volume, but not with PCS infarct volume in AIS. Also, NLR was an independent predictor of 3-month mortality in AIS patient.

Optimal treatment modality for coexisting acute myocardial infarction and ischemic stroke.

The simultaneous occurrence of acute ST-segment elevation myocardial infarction and acute ischemic stroke is an uncommon and complex clinical presentation. Although the medical treatment of both diseases is similar, data regarding optimal reperfusion therapy are limited. Nevertheless, use of tissue plasminogen activator may be a reasonable strategy for treatment of both diseases. We present a rare case of coexisting thrombosis of the coronary artery and mid cerebral artery that was managed successfully with tissue plasminogen activator thrombolytic therapy.

Assessment of relationship between C-reactive protein to albumin ratio and 90-day mortality in patients with acute ischaemic stroke.

AIM AND CLINICAL RATIONALE FOR THE STUDY: It is now known that inflammation is involved in the pathophysiology of acute ischaemic stroke (AIS). It has been proven that CRP and albumin alone are useful in predicting a prognosis for stroke patients. A combination of these two parameters, namely the ratio of CRP to albumin (CAR), is believed to be a more accurate indicator of inflammatory status than CRP or albumin alone, and may be more valuable than either of them separately in predicting the prognosis of ischaemic stroke patients. However, the role of CAR as a predictor of mortality in patients with AIS remains unclear. MATERIALS AND METHODS: We retrospectively enrolled 260 patients who were referred to our clinic within the first 24 hours of symptom presentation and who were diagnosed with AIS between January 2015 and December 2018. The patient group was classified into two groups according to 90-day mortality. These groups were compared in terms of C-reactive protein, albumin, and CAR. RESULTS: The C-reactive protein and CAR values were higher, and the albumin level was lower, in non-surviving patients. The CAR value was also found to be a significant independent variable of 90-day mortality in patients with AIS (p < 0.001). The optimum cut-off value of CAR in predicting the 90-day mortality for patients with AIS was 0.50, with 64.1% sensitivity and 56.2% specificity. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study demonstrated that a high CAR value is an independent predictor of 90-day mortality in patients with AIS.

Acute motor and sensory axonal neuropathy associated with Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease with mononuclear cell infiltration and destruction of the lacrimal gland and salivary glands, which cause dryness of the eyes and mouth. The most common neurological condition seen in SS is peripheral neuropathy. Initial manifestation of SS as an acute fulminant peripheral neuropathy is extremely rare. We report a 42-year-old patient presenting with acute motor sensory-axonal neuropathy in the presence of SS. She showed partial response to intravenous immunoglobulin but favourable clinical improvement was seen after initiation of corticosteroid treatment.

Hyperdense Middle Cerebral Artery Sign Together with Pulmonary Thromboembolism.

BACKGROUND: Hyperdense middle cerebral artery sign is an appearance of the middle cerebral artery on non-contrast-enhanced computed tomography. Embolic occlusion of the pulmonary arterial system is referred to as pulmonary embolism. When pulmonary embolism coexists with a patent foramen ovale, increased pressure in the right atrium may result in widening of the foramen and consequently, cause serious conditions due to paradoxical embolus. Coexistence of hyperdense middle cerebral artery sign and pulmonary thromboembolism is very rare in the literature. CASE REPORT: We presented a 60-year-old female patient who had both hyperdense middle cerebral artery sign and pulmonary thromboembolism. CONCLUSIONS: To our knowledge, togetherness of hyperdense MCA sign and pulmonary thromboembolism is extremely rare in the literature. In our case, we found both pulmonary embolism due to DVT and paradoxical embolism due to existing patent foramen ovale.

Assessment of both serum S-100B protein and neuropeptide-Y levels in childhood breath-holding spells.

OBJECTIVE: Breath-holding spells are common paroxysmal events in children. Although the spells have a benign prognosis in the long term, they may be complicated by loss of consciousness, tonic-clonic movements, and occasionally seizures. Hence, this study aimed to measure the levels of serum S-100B proteins and neuropeptide-Y in the blood of children who experience breath-holding spells. METHODS: The study groups consisted of 45 patients (13 females, 32 males) with breath-holding spells and a control group of 32 healthy individuals (12 females, 20 males). The serum S-100B levels were measured using commercially available ELISA kits. The neuropeptide-Y levels in the serum were measured with RayBio® Human/Mouse/Rat Neuropeptide Y ELISA kits. RESULTS: The mean serum S-100B protein level of the breath-holding spells group was 56.38 ± 13.26 pg/mL, and of the control group, 48.53 ± 16.77 pg/mL. The mean neuropeptide-Y level was 62.29 ± 13.89 pg/mL in the breath-holding spells group and 58.24 ± 12.30 pg/mL in the control group. There were significant differences between the groups with respect to serum S-100B protein levels (p = 0.025), while there was no statistically significant difference in neuropeptide-Y levels between the breath-holding spells group and the control group (p = 0.192). CONCLUSIONS: The findings of this study suggest that frequent and lengthy breath-holding may lead to the development of neuronal metabolic dysfunction or neuronal damage which is most likely related to hypoxia. In light of these findings, future studies should be conducted using biochemical and radiological imaging techniques to support these results.

Assessment of the effectiveness of interferential current therapy and TENS in the management of carpal tunnel syndrome: a randomized controlled study.

We assessed the effectiveness of interferential current (IFC) and transcutaneous electrical nerve stimulation (TENS) therapies in the management of carpal tunnel syndrome (CTS) compared with splint therapy, a standard treatment modality for CTS. This was a prospective, single-blinded, single-center, randomized, three-group parallel intervention study of 3 weeks duration. Efficacy was examined in the third week after the end of treatments. Subjects were assigned randomly to one of three groups: group I patients received splint therapy, group II patients received TENS applied on the palmar surface of the hand and the carpal tunnel, and group III patients underwent IFC therapy applied on the palmar surface of the hand and the volar surface of the forearm. TENS and ICF treatments were applied five times weekly for a total of 15 sessions. Group 1 patients were stabilized with volar wrist splints for 3 weeks. The efficacy of the therapies was assessed before initiation of therapy and at 3 weeks after completion of therapy using a visual analog scale (VAS), a symptom severity scale, the functional capacity scale of the BCTQ, and measurement of median nerve motor distal latency (mMDL) and median sensory nerve conduction velocity (mSNCV). Groups were compared pairwise using the Mann-Whitney U test to identify the source of differences between groups. The Wilcoxon test was used to analyze changes in variables over time within a group. In the VAS, BCTQ, MDL, and mSNCV, no significant difference was observed between the groups (p > 0.05). In the VAS, BCTQ, and mSNCV, statistically significant improvements were detected in all groups (p < 0.05). There was no statistically significant difference between TENS and splint therapy with respect to improvement in clinical scores, whereas IFC therapy provided a significantly greater improvement in VAS, mMDL, and mSNCV values than splint therapy (VAS: 4.80 ± 1.18 and 6.37 ± 1.18; p = 0.001, mMDL: 3.89 ± 0.88 and 4.06 ± 0.61; p = 0.001, mSNCV: 41.80 ± 1.76 and 40.75 ± 1.48; p = 0.010). IFC therapy provided a significantly greater improvement in VAS, symptom severity, functional capacity, and mMDL and mSNCV values than TENS therapy (VAS: 4.80 ± 1.18 and 6.68 ± 1.42; p < 0.001, symptom severity: 2.70 ± 1.03 and 3.37 ± 1.21; p = 0.015, functional capacity: 1.90 ± 1.21 and 2.50 ± 0.78; p = 0.039, mMDL: 3.89 ± 0.88 and 4.06 ± 0.88; p = 0.003, and mSNCV: 41.80 ± 1.76 and 41.38 ± 1.78; p = 0.021). IFC may be considered a new and safe therapeutic option for the treatment of CTS.

Can C-reactive protein/albumin ratio be a prognostic factor in acute stroke patients undergoing mechanical thrombectomy?

INTRODUCTION: C-reactive protein (CRP) and albumin are markers synthesized by the liver and may reflect inflammatory responses. CRP/Albumin ratio (CAR) serves better to reflect the inflammatory state and therefore the prognosis. Worse prognosis is reported in previous studies when CAR rate on admission is high in patients with stroke, aneurysmal subarachnoid hemorrhage, malignancy or patients followed in intensive care units. We aimed to investigate the relation of CAR with prognosis in mechanical thrombectomy performed acute stroke patients. MATERIALS AND METHODS: Stroke patients admitted to five different stroke centers between January 2021 and August 2022 undergoing mechanical thrombectomy were included and retrospectively analyzed. The CAR ratio was calculated as the ratio of CRP to albumin level in the venous blood samples. Primary outcome was the relation between CAR and functional outcome at 90 days determined by modified Rankin Scale (mRS). RESULTS: This study included 558 patients with a mean age of 66,5 ± 12.5 years (age range:18-89 years) best cutoff value of the CAR was 3.36, with 74.2 % sensitivity and 60.7 % specificity (Area under the curve: 0.774; 95 %CI: 0.693-0.794). There was no significant correlation between CAR rate and age, CAR rate and NIHSS on admission, and also between CAR rate and symptom recanalization (p > 0.05). CAR ratio in the mRS 3-6 group was statistically significantly higher (p < 0.001). In the multivariate analyses, CAR showed an association with 90-day mortality (odds ratio, 1.049; 95 % CI, 1.032-1.066) CONCLUSION: In acute ischemic stroke patients treated with mechanical thrombectomy, CAR may be one of the factors affecting poor clinical outcome and/or mortality in patients undergoing mechanical thrombectomy. Upcoming similar studies in this patient group may better clarify the prognostic role of CAR.

Posterior reversible encephalopathy during an attack of familial Mediterranean fever.

Reported here is a 19-year-old female patient with familial Mediterranean fever who was seen for altered mental status and seizures. She was eventually diagnosed to have posterior reversible leukoencephalopathy syndrome. Although a variety of conditions have been reported in association with this syndrome, to our best notice, this is the second case in whom familial Mediterranean fever and posterior reversible leukoencephalopathy coexists.

How to Improve the Management of Acute Ischemic Stroke by Modern Technologies, Artificial Intelligence, and New Treatment Methods.

Stroke remains one of the leading causes of death and disability in Europe. The European Stroke Action Plan (ESAP) defines four main targets for the years 2018 to 2030. The COVID-19 pandemic forced the use of innovative technologies and created pressure to improve internet networks. Moreover, 5G internet network will be helpful for the transfer and collecting of extremely big databases. Nowadays, the speed of internet connection is a limiting factor for robotic systems, which can be controlled and commanded potentially from various places in the world. Innovative technologies can be implemented for acute stroke patient management soon. Artificial intelligence (AI) and robotics are used increasingly often without the exception of medicine. Their implementation can be achieved in every level of stroke care. In this article, all steps of stroke health care processes are discussed in terms of how to improve them (including prehospital diagnosis, consultation, transfer of the patient, diagnosis, techniques of the treatment as well as rehabilitation and usage of AI). New ethical problems have also been discovered. Everything must be aligned to the concept of "time is brain".

The impact of post-dilatation on periprocedural outcomes during carotid artery stenting: A single-center experience.

BACKGROUND AND AIMS: Carotid artery stenting (CAS) is an accepted treatment modality for carotid artery disease. However, CAS is associated with periprocedural embolic events, and the effect of balloon post-dilatation has not been sufficiently investigated in large studies. We assessed the effect of post-dilatation on periprocedural outcomes during CAS. METHODS: The study included 128 patients who underwent CAS. The patients were divided into groups according to whether post-dilatation was (post-dilatation [+], group 1) or was not (post dilatation [-], group 2) performed after stent deployment. Major adverse events were defined as death, minor or major stroke, and transient ischemic attack at 30 days. Silent ischemia was assessed using diffusion-weighted magnetic resonance imaging. RESULTS: No significant between-group differences were found in baseline characteristics, comorbid diseases, or lesion characteristics. The degree of stenosis and procedure duration was greater in group 1 than in group 2. The rate of major adverse events at 30 days was similar between the two groups (5.1% vs. 4.3%, p = 0.844). The silent ischemia rate and number of high-intensity signals were higher in group 1 than in group 2 (45.8% vs. 26.1%, p = 0.020 and 1.01 [1.2] vs. 0.42 [0.79], p = 0.002). Multivariate analysis revealed that post-dilatation was associated with a 2.4-fold increase in silent ischemia (95% confidence interval: 1.15-5.20, p = 0.020). CONCLUSIONS: Although post-dilatation was not associated with an increase in major adverse events, it significantly increased the incidence of periprocedural silent ischemia. Therefore, post-dilation should be performed only in cases with severe residual stenosis after CAS.

Does stroke etiology play a role in predicting outcome of acute stroke patients who underwent endovascular treatment with stent retrievers?

AIMS: The goal of the study was to identify whether the stroke etiology play a role in the recanalization and outcome of patients who underwent mechanical thrombectomy with stent retrievers. METHODS AND RESULTS: A retrospective analysis of a prospectively collected database included consecutive patients treated with stent retrievers. We included patients with cardioembolic stroke and large vessel atherosclerotic disease and compared risk factors for stroke, baseline NIHSS and Alberta Stroke Program Early CT scores (ASPECTS), stroke outcome, recanalization rate, onset-to-recanalization, onset-to-groin puncture time and the procedural time between two groups. Male sex was statistically more common in patients with large vessel atherosclerotic disease. Mean time from symptom onset- to the achievement of recanalization in patients with LVAD was 242±72.4 compared with cardioembolic stroke patients (301±70.7; p=0.014). Time for groin puncture to recanalization was longer in patients with cardioembolic stroke compared to LVAD group (97.5±44.3 vs 58.2±21.8; p=0.002). Time for microcatheter to successful recanalization or procedural termination was longer in patients with cardioembolic stroke compared to LVAD group (63.6±30.2 vs 34.2±19.4; p<0.001) with cardioembolic stroke had significantly worse long-term outcome (mRS 3-6) compared to those with LVAD (60.6% vs 26.3%; p=0.036). CONCLUSION: Stroke etiology may play a role in the outcome of acute stroke patients who underwent endovascular stroke therapy. Cardioembolic strokes may be more resistant to endovascular acute stroke treatment.

An evaluation of serum paraoxonase together with arylesterase activities and oxidative stress in children with intractable epilepsy: a cross-sectional study.

Epilepsy is the most common chronic neurological illness in childhood and adolescence. The aim of this study was to investigate paraoxonase and arylesterase activities along with oxidative status parameters in children with intractable epilepsy. The study comprised 42 subjects with intractable epilepsy and a control group of 35 healthy subjects. Serum paraoxonase and arylesterase activities, and lipid hydroperoxide levels were determined. All paraoxonase and arylesterase activities were significantly lower in the intractable epilepsy subjects than in the controls (P<0.001), whereas lipid hydroperoxide levels were significantly higher (P<0.05). In conclusion, paraoxonase and arylesterase activities were decreased and the lipid hydroperoxide level was increased in patients with intractable epilepsy. These results showed that intractable epilepsy subjects may be more prone to the development of atherosclerosis.