The effect of Jendrassik maneuver on the persistence of the peroneal nerve F-wave.

Objectives: This study investigated whether peroneal nerve F-wave persistence increased when the Jendrassik maneuver (JM) was performed, aiming to obtain information about the physiology of F-waves and JM. Patients and methods: Thirty healthy individuals (HIs; 17 females, 13 males; mean age: 33.6±8.2 years; range, 23-50 years) were included in the prospective experimental study conducted between June 15, 2021, and December 15, 2021. Nerve conduction studies of peroneal, superficial peroneal, posterior tibial, and sural nerves were performed in one extremity of each HI. The peroneal nerve F-wave study was performed at rest (Study 1), during JM (Study 2), and after JM (Study 3). F-wave persistence of the peroneal nerve, maximum F-wave amplitude (ampF-wavemax), mean F-wave amplitude (ampF-wavemean), minimum F-wave latency, and the ratio of ampF-wavemean to maximum M amplitude (F/M ratio) were analyzed. Results: The mean peroneal nerve F-wave persistence in Study 1, Study 2, and Study 3 was 28.7±23.9%, 52.3±32.1%, and 34.7±29.0%, respectively. F-wave persistence in Study 2 was higher compared to Studies 1 and 3 (p<0.001 and p<0.001, respectively). Moreover, ampF-wavemax, ampF-wavemean, and F/M ratio in Study 2 were higher than Studies 1 and 3 (p=0.026 and p=0.021 for ampF-wavemean; p=0.015 and p=0.003 for ampF-wavemax; p=0.033 and p=0.015 for F/M ratio, respectively). F-wave persistence in Study 2 was positively correlated with ampF-wavemax and ampF-wavemean (p<0.001, r= 0.717; p<0.001, r=0.786, respectively). Conclusion: This study demonstrated that JM increased F-wave persistence and amplitude. Jendrassik maneuver may show its effect through motor neuron excitability.

Needle electromyography abnormalities in the upper trapezius muscle in neuromuscular disorders.

BACKGROUND: : Needle electromyography (EMG) abnormalities in the trapezius muscle (TM) can be seen in neuromuscular disorders. The aim was to determine the characteristics of needle EMG abnormalities observed in the TM in neuromuscular disorders. METHODS: The data of patients who applied to the Clinical Neurophysiology Laboratory of University of Health Sciences Adana City Training and Research Hospital between December 2018 and October 2021 were reviewed. Polio survivors, amyotrophic lateral sclerosis (ALS) patients, patients with sensorimotor polyneuropathy, patients with spinal cord lesions involving C2/C3/C4 segments, patients with spinal accessory nerve (SAN) lesions, neuralgic amyotrophy (NA) patients, and patients with myopathy were included. Needle EMG findings of the upper TM of the patients were analyzed. Positive sharp waves, fibrillation potentials, fasciculation potentials, myotonic discharges, and motor unit action potential (MUAP) changes were considered needle EMG abnormalities. RESULTS: Eighty-one polio survivors, 23 ALS patients, 39 patients with sensorimotor polyneuropathy, 10 patients with cervical spinal lesions, eight NA patients, seven patients with SAN lesions, and three patients with myopathy were included in the study. Fifteen (65.2%) ALS patients, 18 (22.2%) polio survivors, three (30%) patients with cervical spinal lesions, two (5.1%) patients with sensorimotor neuropathy, one (12.5%) NA patient, seven (100%) patients with SAN lesions, and two (66.7%) patients with myopathies had at least one needle EMG abnormality in the TM. Fasciculation potentials in the TM were seen in 10 (43.5%) ALS patients. In four patients with SAN lesions and one polio survivor, MUAP could not be obtained from the TM. DISCUSSION: There may be more frequent needle EMG abnormalities, particularly in ALS patients and patients with SAN lesions. Since the number of patients with myopathy included in this study was low, it is difficult to comment on the needle EMG features of the TM for these patients. In addition, this study indicated that fasciculation potentials in the TM are typical in ALS patients and that MUAP may not be obtained from the TM in patients with SAN lesions.

Neuropathic pain in peroneal nerve entrapment at the fibular head.

BACKGROUND: Peroneal neuropathy at the fibular head (PNFH) is a mononeuropathy that typically presents with drop foot and sensory abnormalities over the skin area innervated by the peroneal nerve. OBJECTIVE: The aim of the present study was to evaluate neuropathic pain in patients with PNFH. METHODS: Patients with clinical and electrodiagnostic features consistent with PNFH associated with weight loss, leg postures, or prolonged sleep were included in the present retrospective cohort study. Nerve conduction studies were performed in the bilateral lower extremities of all patients. The Leeds assessment of neuropathic symptoms and signs scale (LANSS) was applied to all patients. RESULTS: Thirty-two PNFH patients (78% males) were included in the study. The LANSS score in the majority of patients was lower than 12. There was 1 patient with a LANSS score of 12. The electrodiagnostic features of 16 patients were compatible with axonal degeneration. The mean LANSS scores of PNFH patients with and without axonal degeneration were 4.3 ± 3.7 and 5.2 ± 2.9, respectively (p = 0.255). CONCLUSION: The present study showed that neuropathic pain is a rare symptom in patients with PNFH associated with weight loss, leg postures, or prolonged sleep.

ANTECEDENTES: A neuropatia fibular na cabeça da fíbula (PNFH) é uma mononeuropatia que normalmente se apresenta com pé caído e anormalidades sensoriais sobre a área da pele inervada pelo nervo fibular. OBJETIVO: O objetivo do presente estudo foi avaliar a dor neuropática em pacientes com PNFH. MéTODOS: Pacientes com características clínicas e eletrodiagnósticas consistentes com PNFH associada a perda de peso, postura das pernas ou sono prolongado foram incluídos neste estudo de coorte retrospectivo. Estudos de condução nervosa foram realizados nas extremidades inferiores bilaterais de todos os pacientes. A escala de avaliação de sintomas e sinais neuropáticos de Leeds (LANSS) foi aplicada a todos os pacientes. RESULTADOS: Trinta e dois pacientes com PNFH (78%) foram incluídos no estudo. A pontuação LANSS em outros pacientes foi menor que 12. Houve 1 paciente com pontuação LANSS de 12. As características eletrodiagnósticas de 16 pacientes foram compatíveis com degeneração axonal. Os escores médios do LANSS de pacientes com PNFH com e sem degeneração axonal foram 4,3 ± 3,7 e 5,2 ± 2,9, respectivamente (p = 0,255). CONCLUSãO: O presente estudo mostrou que a dor neuropática é um sintoma raro em pacientes com PNFH associada à perda de peso, postura das pernas ou sono prolongado.

Neuropathic pain in peroneal nerve entrapment at the fibular head / Dor neuropática no aprisionamento do nervo fibular na cabeça da fíbula

Abstract Background Peroneal neuropathy at the fibular head (PNFH) is a mononeuropathy that typically presents with drop foot and sensory abnormalities over the skin area innervated by the peroneal nerve. Objective The aim of the present study was to evaluate neuropathic pain in patients with PNFH. Methods Patients with clinical and electrodiagnostic features consistent with PNFH associated with weight loss, leg postures, or prolonged sleep were included in the present retrospective cohort study. Nerve conduction studies were performed in the bilateral lower extremities of all patients. The Leeds assessment of neuropathic symptoms and signs scale (LANSS) was applied to all patients. Results Thirty-two PNFH patients (78% males) were included in the study. The LANSS score in the majority of patients was lower than 12. There was 1 patient with a LANSS score of 12. The electrodiagnostic features of 16 patients were compatible with axonal degeneration. The mean LANSS scores of PNFH patients with and without axonal degeneration were 4.3 ± 3.7 and 5.2 ± 2.9, respectively (p = 0.255). Conclusion The present study showed that neuropathic pain is a rare symptom in patients with PNFH associated with weight loss, leg postures, or prolonged sleep.

Resumo Antecedentes A neuropatia fibular na cabeça da fíbula (PNFH) é uma mononeuropatia que normalmente se apresenta com pé caído e anormalidades sensoriais sobre a área da pele inervada pelo nervo fibular. Objetivo O objetivo do presente estudo foi avaliar a dor neuropática em pacientes com PNFH. Métodos Pacientes com características clínicas e eletrodiagnósticas consistentes com PNFH associada a perda de peso, postura das pernas ou sono prolongado foram incluídos neste estudo de coorte retrospectivo. Estudos de condução nervosa foram realizados nas extremidades inferiores bilaterais de todos os pacientes. A escala de avaliação de sintomas e sinais neuropáticos de Leeds (LANSS) foi aplicada a todos os pacientes. Resultados Trinta e dois pacientes com PNFH (78%) foram incluídos no estudo. A pontuação LANSS em outros pacientes foi menor que 12. Houve 1 paciente com pontuação LANSS de 12. As características eletrodiagnósticas de 16 pacientes foram compatíveis com degeneração axonal. Os escores médios do LANSS de pacientes com PNFH com e sem degeneração axonal foram 4,3 ± 3,7 e 5,2 ± 2,9, respectivamente (p = 0,255). Conclusão O presente estudo mostrou que a dor neuropática é um sintoma raro em pacientes com PNFH associada à perda de peso, postura das pernas ou sono prolongado.

COVID-19 can cause blink reflex abnormalities.

Background and purpose: Neurological symptoms and complications associated with coronavirus 2019 (COVID-19) are well known. It was aimed to evaluate the brainstem and trigeminal/facial nerves and the pathways between these structures in COVID-19 using the blink reflex test. Methods: Thirty patients with post COVID-19 (16 males, 14 females) and 30 healthy individuals (17 males, 13 females) were included in this prospective study. Individuals who previously had a positive nose swap polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 and whose previously clinical features were compatible with COVID-19 were included in the post COVID-19 patient group. Neurological examination of the participants should be normal. Blink reflex test was performed on all participants. R1, ipsilateral R2 (IR2), and contralateral R2 (CR2) waves obtained from the test were analyzed. Results: The mean ages of healthy individuals and post COVID-19 patients were 34.0±6.4 and 38.4±10.6 years, respectively. Both age and gender were matched between the groups. R1, IR2, and CR2 latencies/amplitudes were not different between the two groups. The side-to-side R1 latency difference was 0.5±0.3 and 1.0±0.8 ms in healthy individuals and post COVID-19 patients, respectively (p=0.011). One healthy individual and 12 patients with post COVID-19 had at least one abnormal blink reflex parameter (p=0.001). Conclusion: This study showed that COVID-19 may cause subclinical abnormalities in the blink reflex, which includes the trigeminal nerve, the seventh nerve, the brainstem, and pathways between these structures.

The needle electromyography findings in the neurophysiological classification of ulnar neuropathy at the elbow

Background/aim: Although ulnar neuropathy at the elbow (UNE) is the second most common entrapment mononeuropathy, there are few reports on its neurophysiological classification. In this study, we tried to find out the role of needle electromyography (EMG) in the neurophysiological classification of UNE. Materials and methods: UNE patients who met the clinical and neurophysiological diagnostic criteria and healthy individuals were included in this study. Reference values of nerve conduction studies were obtained from healthy individuals. Needle EMG was performed to all UNE patients. According to the neurophysiological classification proposed by Padua, UNE patients were classified as mild, moderate, and severe. Results: Thirty-one controls and thirty-five UNE patients were included in the study. There was mild UNE in 23 patients, moderate UNE in 8, and severe UNE in 4. Abnormal needle EMG findings were present in all patients with moderate and severe UNE and in 12 patients with mild UNE. Conclusion: Abnormal needle EMG findings are seen in most of the UNE patients. Therefore, it is not practical to use needle EMG findings in the neurophysiological classification. Needle EMG abnormalities may also be present in patients with mild UNE due to axonal degeneration or motor conduction block.

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.

Predictors of a Good Outcome after Endovascular Stroke Treatment with Stent Retrievers.

BACKGROUND AND PURPOSE: Successful recanalization after endovascular stroke therapy (EVT) did not translate into a good clinical outcome in randomized trials. The goal of the study was to identify the predictors of a good outcome after mechanical thrombectomy with stent retrievers. METHODS: A retrospective analysis of a prospectively collected database included consecutive patients treated with stent retrievers. We evaluated the influence of risk factors for stroke, baseline NIHSS score, Alberta Stroke Program Early CT (ASPECT) score, recanalization rate, onset-to-recanalization and onset-to-groin puncture time, and glucose levels at admission on good outcomes. The number of stent passes during procedure and symptomatic hemorrhage rate were also recorded. A modified Rankin Scale (mRS) score of 0-2 at 90 days was considered as a good outcome. RESULTS: From January 2011 to 2014, 70 consecutive patients with an acute ischemic stroke underwent EVT with stent retrievers. The absence of a medical history of diabetes was associated with good outcomes. Apart from diabetes, the baseline demographic and clinical characteristics of patients were similar between subjects with poor outcome versus those with good outcomes. Median time from onset to recanalization was significantly shorter in patients with good outcomes 245 (IQR: 216-313 min) compared with poor outcome patients (315 (IQR: 240-360 min); P = 0.023). Symptomatic intracranial hemorrhage was observed in eight (21.6%) of 37 patients with poor outcomes and no symptomatic hemorrhage was seen in patients with good outcomes (P = 0.006). In multivariate stepwise logistic regression analysis, a favorable ASPECT score (ASPECT > 7) and successful recanalization after EVT were predictors of good outcomes. Every 10-year increase was associated with a 3.60-fold decrease in the probability of a good outcome at 3 months. The probability of a good outcome decreases by 1.43-fold for each 20 mg/dL increase in the blood glucose at admission. CONCLUSION: To achieve a good outcome after EVT with stent retrievers, quick and complete recanalization and better strategies for patient selection are warranted. We need randomized trials to identify the significance of tight blood glucose control in clinical outcome during or after EVT.

Hypertension alters phosphorylation of VASP in brain endothelial cells.

Hypertension impairs cerebral vascular function. Vasodilator-stimulated phosphoprotein (VASP) mediates active reorganization of the cytoskeleton via membrane ruffling, aggregation and tethering of actin filaments. VASP regulation of endothelial barrier function has been demonstrated by studies using VASP(-/-) animals under conditions associated with tissue hypoxia. We hypothesize that hypertension regulates VASP expression and/or phosphorylation in endothelial cells, thereby contributing to dysfunction in the cerebral vasculature. Because exercise has direct and indirect salutary effects on vascular systems that have been damaged by hypertension, we also investigated the effect of exercise on maintenance of VASP expression and/or phosphorylation. We used immunohistochemistry, Western blotting and immunocytochemistry to examine the effect of hypertension on VASP expression and phosphorylation in brain endothelial cells in normotensive [Wistar-Kyoto (WKY)] and spontaneously hypertensive (SH) rats under normal and exercise conditions. In addition, we analyzed VASP regulation in normoxia- and hypoxia-induced endothelial cells. Brain endothelial cells exhibited significantly lower VASP immunoreactivity and phosphorylation at the Ser157 residue in SHR versus WKY rats. Exercise reversed hypertension-induced alterations in VASP phosphorylation. Western blotting and immunocytochemistry indicated reduction in VASP phosphorylation in hypoxic versus normoxic endothelial cells. These results suggest that diminished VASP expression and/or Ser157 phosphorylation mediates endothelial changes associated with hypertension and exercise may normalize these changes, at least in part, by restoring VASP phosphorylation.

CKD is associated with recurrent ischemia but not with hemorrhagic transformation in acute ischemic stroke patients.

BACKGROUND: We investigated the associations of Recurrent Ischemic Stroke (RIS) and Hemorrhagic Transformation (HT) with CKD in acute ischemic stroke patients. METHOD: The subjects were 160 patients, divided into two groups: with eGFR <60 mL/min/1.73 m2 (CKD), with eGFR ≥60 mL/min/1.73 m2 (without CKD). RESULTS: Subjects having DM (p = 0.018), CKD (p = 0.025) and treated with ACEI/ARB (p = 0.039) revealed association with RIS. Regression analysis disclosed only CKD (p = 0.04). Carotid artery stenosis (p = 0.030) and serum calcium levels (p = 0.013) showed significant association with HT. CONCLUSION: Our results disclosed that CKD could be a risk factor for RIS. There is no relation between CKD and HT.

Therapeutic Plasma Exchange in Neurologic Diseases: An Experience with 91 Patients in Seven Years.

INTRODUCTION: In this study, we report the results of our experience of therapeutic plasma exchange (TPE) for neuroimmunologic disorders performed at our hospital over a seven-year period. METHODS: We retrospectively reviewed the medical records of 91 patients (53 male, 38 female) who had been treated at our center with TPE. RESULTS: 60 patients with Guillain-Barrè syndrome (GBS), 23 with myasthenia gravis (MG), 4 with chronic inflammatory demyelinating polyneuropathy (CIDP) and 1 patient each with polymyositis, septic encephalopathy, acute disseminated encephalomyelitis (ADEM) and Opsoclonus-Myoclonus syndrome (OMS) received TPE. 26.7% of GBS patient's made complete recovery, 61.7% had partial recovery and 11.7% patients died due to respiratory failure. Despite our best efforts and effective TPE treatments, 13.4% of MG patients deceased, however, 78% had full recovery. Three patients with CIDP were discharged with full and 1 patient with partial recovery. The patient with ADEM had partial recovery with TPE at first, but deceased 2 months later due to pneumonia-related respiratory insufficiency. While, patient with polymyositis had slight-partial recovery, we obtained full recovery with TPE in septic encephalopathy and OMS patients. The side effects and complications of treatments with TPE, which included hypotension, hypocalcaemia and anemia, were mild and manageable. CONCLUSION: The improvement rates were encouraging and we concluded that significant benefit can be achieved with TPE for the treatment of neuroimmunological disorders.

Impact of early versus late enteral nutrition on cell mediated immunity and its relationship with glucagon like peptide-1 in intensive care unit patients: a prospective study.

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) originates from the gastrointestinal system in response to the presence of nutrition in the intestinal lumen and potentiates postprandial insulin secretion. Also, it acts as an immune-modulator which has influences on cell-mediated immunity. MATERIALS AND METHODS: The study was designed as a prospective, single-blinded study and carried out in the neurology intensive care unit (ICU) of a university hospital. Twenty-four naive patients with acute thromboembolic cerebrovascular events, with National Institute of Health (NIH) stroke scores between 12 and 16, were included. Any condition interfering with GLP-1 and immunity was regarded as exclusion criterion. Two patients died, and two dropped out of the study due to complicating conditions. RESULTS: Group 1 and Group 2 exhibited similar GLP-1 levels in the pre-feeding and post-feeding periods for both the first time and the third day of enteral feeding. Also, no significant change in pre-/post-feeding GLP-1 levels was observed within groups. T-helper and T-regulatory cells increased, T-cytotoxic cells decreased significantly in Group 1 (P=0.02; P=0.036; P=0.0019), but remained the same in Group 2 after enteral feeding. Positive but statistically insignificant clinical effects in terms of predisposition to infections (10% vs 40%) and median time of ICU stay (10 vs 15 days) were observed in Group 1. CONCLUSIONS: Depending on our findings, we propose that early enteral feeding may cause amelioration in cell-mediated immunity via factors other than GLP-1 in ICU patients with acute thromboembolic stroke. However, the possible deleterious effects of parenteral nutrition cannot be ruled out.

[Neurological involvement in brucellosis; clinical classification, treatment and results]. / Brusellozda sinir sistemi tutulumu; klinik siniflama, tedavi ve sonuçlar.

The aim of this retrospective study was to describe and to categorize different clinical pictures of patients with neurobrucellosis in our clinic, and present demographical and laboratory data about the patients. Hospital records of 430 patients with brucellosis between 2003 and 2009, were retrospectively reviewed. Out of 430 patients, 19 (4.4%) had neurobrucellosis. These patients were classified into four groups: Meningitis group (n= 14, 13 cases of subacute/chronic meningitis, one case of acute meningitis), encephalomyelitis group (n= 3, one case of meningoencephalomyelitis, one case of cerebellar abscess and one case of transverse myelitis), polyradicular group (n= 1, Miller-Fisher Syndrome), and others (n= 1, one case of intradural abscess). Ten patients (52.6%) were female, and the mean age of the patients was 48.8 years. About 47.4% of the patients had fever, 26% of the patients had neck stiffness and 5% of the patients were in an unconscious state. Out of 19 patients, 18 underwent lumbar puncture and they had positive brucella antibody test in cerebrospinal fluid (CSF) by standard tube agglutination method. Brucella spp. Were grown in four patient's blood culture and one patient's CSF culture. There were cranial nerve involvement in five cases, the most frequent being the sixth cranial nerve. Out of 19 patients, three recovered with sequela (paraparesis, hearing loss, dementia and sphincter disfunction) and 16 patients recovered completely. Although neurobrucellosis is most frequently presented as subacute/chronic meningitis, it may be associated with different clinical pictures. The classical triad of meningitis (fever, neck stiffness, unconsciousness) is rarely seen in brucellosis-related meningitis. Brucellosis should be kept in mind in patients with unexplained neurological findings particularly in areas where brucellosis is endemic. In addition, a current classification of neurobrucellosis, related to involved location of nervous system, clinical picture and pathogenesis, is needed.

Recurrent ischemic stroke as an initial manifestation of an concealed pancreatic adenocarcinoma: Trousseau's syndrome.

In rare instances, stroke may precede a diagnosis of cancer and be the first clinical evidence of an underlying malignancy.Cerebral infarction mostly complicates lymphomas, carcinomas, and solid tumors. Malignancy-related thromboembolism can present as acute cerebral infarction, nonbacterial thrombotic endocarditis and migratory thrombophlebitis. It is generally attributed to a cancer-related hypercoagulable period, chronic disseminated intravascular coagulopathy (DIC), or tumor embolism. We reported a case of malignancy-related thromboembolism from an undiagnosed pancreatic adenocarcinoma in a 54-year-old man, who presented with recurrent ischemic stroke due to chronic DIC. He died of the underlying malignancy despite the appropriate institution of anticoagulation therapy.This case emphasizes that cerebral infarction may be the first manifestation of an undiagnosed cancer. If there is laboratory or clinical evidence associated with DIC, patients with a cerebral infarct of an unknown etiology should be investigated for a malignant process. The optimal method of anticoagulation in cancer patients with thromboembolic disease (TED) remains unclear.

Genome-wide association study of intracranial aneurysm identifies three new risk loci.

Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with approximately 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 x 10(-12)), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 x 10(-9)) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 x 10(-9)). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 x 10(-12)) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 x 10(-22)). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy.

Congenital ataxia with cerebellar hypoplasia is a heterogeneous group of disorders that presents with motor disability, hypotonia, incoordination, and impaired motor development. Among these, disequilibrium syndrome describes a constellation of findings including non-progressive cerebellar ataxia, mental retardation, and cerebellar hypoplasia following an autosomal recessive pattern of inheritance and can be caused by mutations in the Very Low Density Lipoprotein Receptor (VLDLR). Interestingly, while the majority of patients with VLDL-associated cerebellar hypoplasia in the literature use bipedal gait, the previously reported patients of Turkish decent have demonstrated similar neurological sequelae, but rely on quadrupedal gait. We present a consanguinous Turkish family with two siblings with cerebellar atrophy, predominantly frontal pachygyria and ataxic bipedal gait, who were found to have a novel homozygous deletion in the VLDLR gene identified by using high-density single nucleotide polymorphism microarrays for homozygosity mapping and identification of CNVs within these regions. Discovery of disease causing homozygous deletions in the present Turkish family capable of maintaining bipedal movement exemplifies the phenotypic heterogeneity of VLDLR-associated cerebellar hypoplasia and ataxia.

Four novel SCN1A mutations in Turkish patients with severe myoclonic epilepsy of infancy (SMEI).

Severe myoclonic epilepsy of infancy (SMEI) (OMIM #607208), also known as Dravet syndrome, is a rare genetic disorder characterized by frequent generalized, unilateral clonic or tonic-clonic seizures that begin during the first year of life. Heterozygous de novo mutations in the SCN1A gene, which encodes the neuronal voltage-gated sodium channel α subunit type 1 (Nav1.1), are responsible for Dravet syndrome, with a broad spectrum of mutations and rearrangements having been reported. In this study, the authors present 4 novel mutations and confirm 2 previously identified mutations in the SCN1A gene found in a cohort of Turkish patients with Dravet syndrome. Mutational analysis of other responsible genes, GABRG2 and PCDH19, were unrevealing. The authors' findings add to the known spectrum of mutations responsible for this disease phenotype and once again reinforce our understanding of the allelic heterogeneity of this disease.

Susceptibility loci for intracranial aneurysm in European and Japanese populations.

Stroke is the world's third leading cause of death. One cause of stroke, intracranial aneurysm, affects approximately 2% of the population and accounts for 500,000 hemorrhagic strokes annually in mid-life (median age 50), most often resulting in death or severe neurological impairment. The pathogenesis of intracranial aneurysm is unknown, and because catastrophic hemorrhage is commonly the first sign of disease, early identification is essential. We carried out a multistage genome-wide association study (GWAS) of Finnish, Dutch and Japanese cohorts including over 2,100 intracranial aneurysm cases and 8,000 controls. Genome-wide genotyping of the European cohorts and replication studies in the Japanese cohort identified common SNPs on chromosomes 2q, 8q and 9p that show significant association with intracranial aneurysm with odds ratios 1.24-1.36. The loci on 2q and 8q are new, whereas the 9p locus was previously found to be associated with arterial diseases, including intracranial aneurysm. Associated SNPs on 8q likely act via SOX17, which is required for formation and maintenance of endothelial cells, suggesting a role in development and repair of the vasculature; CDKN2A at 9p may have a similar role. These findings have implications for the pathophysiology, diagnosis and therapy of intracranial aneurysm.