Life-threatening parkinsonism-hyperpyrexia syndrome following bilateral deep brain stimulation of the subthalamic nucleus

Parkinsonism-hyperpyrexia syndrome (PHS), or neuroleptic malignant syndrome (NMS), is a neurophysiologic reaction to the acute withdrawal/decrease of central dopamine levels. It is a severe complication characterized by rigidity, change in consciousness level, fever, hypertension, and autonomic instability, that can be fatal. To the best of our knowledge, PHS following deep brain stimulation (DBS) of subthalamic nucleus (STN) surgery due to anti-Parkinson drug discontinuation has been previously reported only six times. Half of these cases resulted in fatalities. Herein, we report on an early diagnosed case of PHS following bilateral STN-DBS which was successfully treated with the administration of dopamine agonists, fluid replacement, and activation of DBS

Clinical and genetic spectrum of an orphan disease MPAN: a series with new variants and a novel phenotype

Introduction. Pathogenic variations in C19orf12 are responsible for two allelic diseases: mitochondrial membrane protein-associated neurodegeneration (MPAN); and spastic paraplegia type 43 (SPG43). MPAN is an orphan disease, which presents with spasticity, dystonia, peripheral nerve involvement, and dementia. The pattern of iron accumulation on brain MRI may be a clue for the diagnosis of MPAN. SPG43, on the other hand, is characterised by progressive lower limb spasticity without brain iron accumulation. We here present clinical and genetic findings of MPAN patients with potentially pathogenic C19orf12 variants.Materials and methods. Patients from 13 different families having progressive motor symptoms with irritative pyramidal signs and brain iron accumulation were screened for C19orf12 gene variants.Results. C19orf12 screening identified seven variants associated with MPAN in eight patients from seven families. We associated two pathogenic variants (c.24G > C; p.(Lys8Asn) and c.194G > A; p.(Gly65Glu)) with the MPAN phenotype for the first time. We also provided a genetic diagnosis for a patient with an atypical MPAN presentation. The variant c.32C > T; p.(Thr11Met), common to Turkish adult-onset MPAN patients, was also detected in two unrelated late-onset MPAN patients.Conclusions. Genetic analysis along with thorough clinical analysis supported by radiological findings will aid the differential diagnosis of MPAN within the neurodegeneration with brain iron accumulation spectrum as well as other disorders including hereditary spastic paraplegia. Dystonia and parkinsonism may not be the leading clinical findings in MPAN patients, as these are absent in the atypical case. Finally, we emphasise that the existence of frameshifting variants may bias the age of onset toward childhood

Cerebral Palsy and Genetics

11-22

Idiopathic Intracranial Hypertension: Diagnosis and Therapeutic Approach

İdiyopatik intrakraniyal hipertansiyon (İİH) sekonder bir nedene bağlı olmayan kafa içi basınç artışıdır. Sıklıkla genç ve obez kadınlarda görülür. Baş ağrısı, görme problemleri ve pulsatil kulak çınlaması hastaları en çok hekime götüren şikayetlerdir. İİH heterojen bulgu ve belirtileri nedeniyle aile hekimlerini ve birçok branşı birlikte ilgilendirmektedir. Tedavisi gecikirse kalıcı morbidite yaratan bu hastalıkta her olgu için kişiye özgü bir tedavi planlanmalıdır. Bu yazıda son yayınlar çerçevesinde İİH'nin etiyopatogenezi ile birlikte tanı ve tedavisi gözden geçirilmiştirIdiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure without a secondary etiology. IIH is seen frequently in young and obese women. Headache, vision problems, and pulsatile tinnitus are the most common symptoms that lead patients to physicians. IIH requires a multidisciplinary approach because it could create permanent morbidity and its treatment plan should be individualized for each patient. The aim of this review was to provide an updated overview of IIH’s pathogenesis, diagnostic criteria, and treatment strategie

De novo 8p23.1 deletion in a patient with absence epilepsy

Çapan Yalçın, Özlem (Arel Author)The 8p23.1 deletion syndrome is a rare multisystem disorder with high penetrance and a variable phenotypic spectrum that includes congenital heart disease (CHD), intellectual disability, behavioural problems, microcephalia, and sometimes epilepsy. Genomic copy number variations (CNVs) constitute an important genetic risk factor for common genetic generalised epilepsy syndromes (GGEs) and absence seizures. These variations, resulting either from copy loss (microdeletion) or copy gain (duplications), disrupt genes associated with neuronal development. Herein, we report an epilepsy patient who was affected by developmental delay, microcephalia, behavioural problems, CHD, and childhood-onset absence seizures. The patient had a 4-Mb de novo microdeletion at 8p23.1. Some of the genes in this region, particularly XKR6 and MIR597, may be involved in the pathogenesis of absence seizures, suggesting that epilepsy may possibly be part of the phenotypic spectrum of the syndrome rather than a comorbid disorder. Thus, CNV screening for GG Eplus patients may have important implications in clinical practice with regards to diagnostic classification, clinical management of the syndromic multisystem disorders, and, potentially, genetic counselling

Is hypoxia a cause or a consequence? The medico-legal considerations of neonatal encephalopathy and cerebral palsy

Neonatal encephalopathy (NE) occurs in the first month after birth of infants and progresses with seizures, respiratory depression and hypotonia. NE is multifactorial, however hypoxia is the first considered cause. Our study aims to discuss medicolegal processes behind the etiological and clinical features of NE and cerebral palsy (CP) over cases evaluated by the specialized board of malpractice of the Council of Forensic Medicine. The 130 cases in the judicial process claimed to be from lack of oxygen at birth, were evaluated retrospectively. The cases were categorized into two groups as evidenced with hypoxic-ischemic encephalopathy (HIE) and not evaluated evidence with HIE, by using blood gas evaluations and brain MRI findings. All risk factors related to labor, resuscitation, intubation, and referral to other NICUs, and presence of seizure were documented in both groups. We found no evidence of intrapartum hypoxia in about 70% of NE and it is suggesting that the causes of NE may have started in the antepartum period. It is necessary to focus on other inherent diseases that play a role in the etiology in medicolegal process, as well as investigate the presence of hypoxia and whether the correct intervention is made

Clinical and genetic features of PKAN patients in a tertiary centre in Turkey

Objective: Pantothenate kinase-associated neurodegeneration (PKAN) is caused by mutations of the pantothenate kinase 2 (PANK2) gene. The major clinical sign of PKAN is dystonia and the eye-of-the-tiger pattern on the MRI has been a clue for the diagnosis. We aim to discuss clinical and genetic findings of 22 PKAN patients from 13 families. Methods: Twenty-two patients were clinically diagnosed with PKAN and screened for PANK2 mutations. The patients were classified according to their onset age and progression rate. Results: Mutation screening revealed 5 novel and 7 previously reported sequence variants in PANK2. The variants identified were in the form of missense changes, small exonic deletions and intronic mutations with a probable splicing effect. The presenting features were dystonia and gait disturbance in early onset patients, whereas the presenting symptoms were variable for the late onset group. The progression rate of the disease was not uniform. Conclusion: The current report is the first patient series of PI(AN from Turkey that expands the clinical and genetic spectrum of the disease. (C) 2017 Elsevier B.V. All rights reserved.Scientific Research Projects Coordination Unit of Istanbul UniversityIstanbul University [51985]; Istanbul Development AgencyTurkiye Cumhuriyeti Kalkinma Bakanligi [TR10/15/YNK/0093]The authors are grateful to the patients and their relatives for their participation in this study. This work was supported by grants from the Scientific Research Projects Coordination Unit of Istanbul University, Project Number 51985, and the Istanbul Development Agency, Project Number TR10/15/YNK/0093. We thank the Advanced Genomics and Bioinformatics Research Centre (IGBAM), TUBITAK-BILGEM, for kindly providing the exome sequencing data of 350 individuals from Turkey with varying disorders, which were used as a population control set for the novel PANK2 mutations. We also thank Dr. Thomas Klopstock and Dr. Holger Prokisch for their help in enrolling the patients in the TIRCON study