Search

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p p = 0.001) and females (OR = 3.0, p p = 0.001), absence seizures (OR = 6.0, p p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation.

Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport, or degradation of neurotransmitters or cofactors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and behavior, the data of 148 patients in the registry of the International Working Group on Neurotransmitter Related Disorders (iNTD) was evaluated using results from standardized age-adjusted tests and questionnaires. Patients with a primary disorder of monoamine metabolism had lower IQ scores (mean IQ 58, range 40-100) within the range of cognitive impairment (, Dietmar Hopp Stiftung (DE); Medical Faculty of the University of Heidelberg.

The trigeminocardiac reflex (TCR) is triggered by stimulation of a branch of the trigeminal nerve and results in vagally mediated bradycardia, hypotension, apnea, and gastrointestinal hypermotility. In the operating theatre, patients susceptible to TCR are typically under general anesthesia; thus, cardiac abnormalities are the most common manifestation. Our case highlights the less common intraoperative manifestations of gastric hypermotility and apnea in a patient undergoing awake craniotomy for tumor resection. Prompt recognition, removal of stimuli, and airway management prevented catastrophic complications while facilitating completion of the procedure.

Intraoperative neurophysiologic monitoring (IONM) includes various neurophysiologic tests which assess the functional integrity of the central and peripheral nervous systems during surgical procedures which place these structures at risk for iatrogenic injury. The rational for using IONM is to provide timely feedback of changes in neural function to enable the reversal of such insult before the development of irreversible neural injury. There are various causes of intraoperative loss of neuromonitoring signals and it is important to systematically rule out all possible causes quickly and thoroughly in order to target the cause of signal loss, correct it and take measures to prevent the same in the future. One such rare cause, is targeted and pressurized cold (room temperature) irrigation of the surgical site, which may induce irritation and vasospasm leading to ischemia of the affected portion of the spinal cord, hence leading to signal changes. We present this case to stress the importance of having knowledgeable members of the team who are well acquainted with all aspects of monitoring in close proximity to the operating room, so as to minimize troubleshooting time. Furthermore, we suggest the use of warm (body temperature) saline during irrigation to the surgical site, especially when using pressurized irrigation systems.

Juvenile myoclonic epilepsy (JME) constitutes about 10% of all epilepsies. Because of executive dysfunction, people with JME may be prone to impulsivity and risk-taking behavior. Our aim was to investigate whether psychosocial issues associated with impulsivity are more prominent in people with JME than in those with other types of genetic generalized epilepsy (GGE). Patients with GGE were recruited retrospectively through the Drammen Hospital records in Buskerud County, Norway, 1999–2013. They were invited to a semi-structured interview, either at the hospital or at home. Ninety-two patients with JME and 45 with other types of GGE were interviewed. Variables were evaluated in terms of their association with JME versus other GGE diagnosis using a logistic regression model. Juvenile myoclonic epilepsy was associated with use of illicit recreational drugs and police charges, although with borderline significance (odds ratio [OR] 3.4, p = 0.087 and OR 4.2, p = 0.095); JME was also associated with being examined for attention-deficit hyperactivity disorder (ADHD) in females (OR 15.5, p = 0.015), a biological parent with challenges like addiction or violent behavior (OR 3.5, p = 0.032), and use of levetiracetam (OR 5.1, p = 0.014). After controlling for group differences, we found psychosocial complications to be associated with JME, potentially influencing the lives of the individuals and their families to a greater extent than the seizures per se. Thus, JME should be considered a disorder of the brain in a broader sense than a condition with seizures only.

RM; Trastornos hereditarios de neurotransmisores; Monoaminas; Deficiencia de tetrahidrobiopterina RM; Trastorns dels neurotransmissors heretats; Monoamines; Deficiència de tetrahidrobiopterina MRI; Inherited neurotransmitter disorders; Monoamines; Tetrahydrobiopterin deficiency; Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analyzed brain MRIs in order to characterize and better understand neuroimaging changes and to re-evaluate the diagnostic role of brain MRI in iMNDs. 81 MRIs of 70 patients (0.1-52.9 years, 39 patients with tetrahydrobiopterin deficiencies, 31 with primary disorders of monoamine metabolism) were retrospectively analyzed and clinical records reviewed. 33/70 patients had MRI changes, most commonly atrophy (n = 24). Eight patients, six with dihydropteridine reductase deficiency (DHPR), had a common pattern of bilateral parieto-occipital and to a lesser extent frontal and/or cerebellar changes in arterial watershed zones. Two patients imaged after acute severe encephalopathy had signs of profound hypoxic-ischemic injury and a combination of deep gray matter and watershed injury (aromatic l-amino acid decarboxylase (AADCD), tyrosine hydroxylase deficiency (THD)). Four patients had myelination delay (AADCD; THD); two had changes characteristic of post-infantile onset neuronal disease (AADCD, monoamine oxidase A deficiency), and nine T2-hyperintensity of central tegmental tracts. iMNDs are associated with MRI patterns consistent with chronic effects of a neuronal disorder and signs of repetitive injury to cerebral and cerebellar watershed areas, in particular in DHPRD. These will be helpful in the (neuroradiological) differential diagnosis of children with unknown disorders and monitoring of iMNDs. We hypothesize that deficiency of catecholamines and/or tetrahydrobiopterin increase the incidence of and the CNS susceptibility to vascular dysfunction.

Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders., We thank all patients and their families for their contributions to this study and for their trust. T.H. and J.K. were supported the grant from the Ministry of Health of the Czech Republic RVO-VFN 64165 GJIH-0599-00-7-846 and ProgresQ26/LF1. A.G.C. and N.J.P. are supported by FIS P118/00111 “Instituto de Salud Carlos III (ISCIII)” and “Fondo Europeo de desarrollo regional (FEDER)”. T.O., K.J., G.F.H. and O.K.H. were supported in parts by the Dietmar Hopp Foundation, St. Leon-Rot, Germany. M.A.K. is funded by an NIHR Professorship, the Sir Jules Thorn Award for Biomedical Research and the Rosetrees trust. M.V. is supported by Stichting Stofwisselkracht Grant. D.H. acknowledges funding by the Molecular Diagnostics Program of the National Center for Tumor Diseases (NCT) Heidelberg.

International audience; Spastic paraplegia type 5 (SPG5/HSP-CYP7B1) is an autosomal recessive hereditary spastic paraplegia (HSP) caused by biallelic variants in the CYP7B1 gene, resulting in dysfunction of the enzyme oxysterol-7-α-hydroxylase. The consequent accumulation of hydroxycholesterols in plasma seems to be pathognomonic for SPG5, and represent a possible target for treatment. We aimed to characterize Norwegian patients with SPG5, including clinical examinations, genetic analyses, measurements of hydroxycholesterols, electrophysiological investigations and brain imaging. Five unrelated patients carried presumed disease-causing variants in CYP7B1, three of the variants were novel. Four patients presented with pure HSP, one with complex HSP. The three tested patients all had markedly increased levels of 25- and 27-hydroxycholesterol in plasma. Our results suggest that the clinical examination is still the best approach to classify disease severity in patients with SPG5. Plasma hydroxycholesterols were elevated, thus presenting as potentially valuable diagnostic biomarkers, in particular in patients where genetic analyses are inconclusive.

Administration of rocuronium to facilitate intubation has traditionally been regarded as acceptable for intraoperative motor evoked potential (MEP) monitoring because of sufficiently rapid spontaneous neuromuscular blockade recovery. We hypothesized that residual neuromuscular blockade, in an amount that could hinder optimal neuromonitoring in patients undergoing intracranial aneurysm clipping, was still present at dural opening. We sought to identify how often this was occurring and to identify factors which may contribute to prolonged blockade. Records of 97 patients were retrospectively analyzed. Rocuronium was administered to facilitate intubation with no additional neuromuscular blockade given. Prolonged spontaneous recovery time to a train-of-four (TOF) ratio of 0.75 after rocuronium administration was defined as 120 min, which was approximately when dural opening and the setting of baseline MEPs were occurring. Logistic regression analysis was used to identify factors related to prolonged spontaneous recovery time. Prolonged spontaneous recovery time to a TOF ratio of 0.75 was observed in 44.3% of patients. Multivariable analysis showed that only the dosage of rocuronium based on ideal body weight had a positive correlation with prolonged spontaneous recovery time (P = 0.01). There was no significant association between dosage of rocuronium based on total body weight, age, sex, or body temperature and prolonged recovery time. This study demonstrates that the duration of relaxation for MEP monitoring purposes is well-beyond the routinely recognized clinical duration of rocuronium. Residual neuromuscular blockade could result in lower amplitude MEP signals and/or lead to higher required MEP stimulus intensities which can both compromise monitoring sensitivity.

Various complications of prone positioning in spine surgery have been described in the literature. Patients in the prone position for extended periods are subject to neurological deficits and/or loss of intraoperative signals due to compression neuropathies, but positioning-related spinal deficits are rare in the thoracolumbar deformity population. The authors present a case of severe kyphoscoliotic deformity with critical thoracolumbar stenosis in which, during the use of a hinged open frame in the prone position, complete loss of intraoperative neural monitoring signals occurred while the frame was flexed into kyphosis to facilitate exposure and instrumentation placement. When the frame was reset to a neutral position, evoked potentials returned to baseline and the operation proceeded without complications. This case represents, to the authors’ knowledge, the first report of loss of evoked potentials due to an alteration of prone positioning on a hinged open frame. When positioning patients in such a manner, careful attention should be directed to intraoperative signals in patients with critical stenosis and kyphotic deformity.

Background Multilevel spine fusion surgery for adult deformity correction is associated with significant blood loss and coagulopathy. Tranexamic acid reduces blood loss in high-risk surgery, but the efficacy of a low-dose regimen is unknown. Methods Sixty-one patients undergoing multilevel complex spinal fusion with and without osteotomies were randomly assigned to receive low-dose tranexamic acid (10 mg/kg loading dose, then 1 mg·kg−1·hr−1 throughout surgery) or placebo. The primary outcome was the total volume of red blood cells transfused intraoperatively. Results Thirty-one patients received tranexamic acid, and 30 patients received placebo. Patient demographics, risk of major transfusion, preoperative hemoglobin, and surgical risk of the 2 groups were similar. There was a significant decrease in total volume of red blood cells transfused (placebo group median 1460 mL vs. tranexamic acid group 1140 mL; median difference 463 mL, 95% confidence interval 15 to 914 mL, P = 0.034), with a decrease in cell saver transfusion (placebo group median 490 mL vs. tranexamic acid group 256 mL; median difference 166 mL, 95% confidence interval 0 to 368 mL, P = 0.042). The decrease in packed red blood cell transfusion did not reach statistical significance (placebo group median 1050 mL vs. tranexamic acid group 600 mL; median difference 300 mL, 95% confidence interval 0 to 600 mL, P = 0.097). Conclusions Our results support the use of low-dose tranexamic acid during complex multilevel spine fusion surgery to decrease total red blood cell transfusion.

Background and purpose Patients with juvenile myoclonus epilepsy (JME) may experience uncontrolled seizures and challenges regarding adherence. Implementation of therapeutic drug monitoring (TDM) may contribute to individualization of the therapy with antiepileptic drugs (AEDs). The purpose of this study was to investigate how the treatment of patients with JME is monitored and to demonstrate pharmacokinetic variability within and between patients with a long-term TDM approach. Method Retrospective data from patients with JME from the TDM-database at Drammen Hospital and the National Center for Epilepsy in Norway (2007–2018) were included. Results Data from 80 of 90 patients with JME using AEDs with TDM measurements was included (88%, 49/31 women/men aged 14–39). One third (27, 33%) was seizure free, 19 (24%) had generalized tonic-clonic seizures, and 53 (66%) myoclonic seizures during the last year. The most common AEDs measured included lamotrigine, valproate, and levetiracetam. Long-term TDM demonstrated variability over time expressed as intra-patient median values and inter-patient ranges of 19% (7–47) for valproate, 43% (10–83) for lamotrigine and 35% (6–111) for levetiracetam. Fifteen pecent (83/563) of serum concentrations were below the reference ranges and clould be due to variable adherence. Comedication with valproate for lamotrigine and pregnancy contributed to variability. The applicability is illustrated in a case of 10 years’ follow-up in a young woman. Conclusion There was extensive pharmacokinetic variability of AEDs in and between patients with JME. A long-term TDM approach may contribute to closer monitoring of patients with JME and be used as a practical tool during clinical consultations.

The article Is the new ASNM intraoperative neuromonitoring supervision "guideline" a trustworthy guideline? A commentary, written by Stanley A. Skinner, Elif Ilgaz Aydinlar, Lawrence F. Borges, Bob S. Carter, Bradford L. Currier, Vedran Deletis, Charles Dong, John Paul Dormans, Gea Drost, Isabel Fernandez‑Conejero, E. Matthew Hoffman, Robert N. Holdefer, Paulo Andre Teixeira Kimaid, Antoun Koht, Karl F. Kothbauer, David B. MacDonald, John J. McAuliffe III, David E. Morledge, Susan H. Morris, Jonathan Norton, Klaus Novak, Kyung Seok Park, Joseph H. Perra, Julian Prell, David M. Rippe, Francesco Sala, Daniel M. Schwartz, Martín J. Segura, Kathleen Seidel, Christoph Seubert, Mirela V. Simon, Francisco Soto, Jeffrey A. Strommen, Andrea Szelenyi, Armando Tello, Sedat Ulkatan, Javier Urriza and Marshall Wilkinson, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 05 January 2019 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 30 January 2019 to © The Author(s) 2019 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The original article has been corrected.

Background Patients with juvenile myoclonic epilepsy (JME) may have uncontrolled seizures. The purpose of this study was to investigate the use and challenges with antiepileptic drugs (AEDs) and the patients' view of these challenges. Method A questionnaire about the use of AEDs, adherence to therapy, and quality of life was given to patients with JME recruited from Drammen Hospital. Data regarding AEDs were confirmed from medical records at Drammen Hospital, Norway (2007–2018). Additional clinical interviews were performed, and a mixed method approach was applied. Results Ninety patients with defined JME diagnosis, 54/36 women/men aged 14–39 (mean: 25) years, were included. Only 29 (33%) were seizure-free. Within the last year, 21% experienced generalized tonic–clonic seizures (GTCS), and 68% had myoclonic jerks. Seventy-six (84%) used AEDs, 78% in monotherapy. A total of 10 AEDs were used;: most commonly valproate (n = 33), lamotrigine (n = 27), and levetiracetam (n = 21). Two-thirds of valproate users were men while all other AEDs were used more in females than in men. Valproate and levetiracetam displayed better efficacy against GTCS than lamotrigine. One-third often/sometimes forgot their medication nonintentionally while 14% had intentional poor adherence. The majority reported good quality of life (76%). No significant correlations between the use of AEDs, use of valproate, poor adherence, quality of life score, and seizure freedom were demonstrated. Half of the patients had serum concentrations measured every year, and two-thirds thought this was important. Qualitative interviews elucidated treatment challenges in JME;, adverse effect burden, adherence, and activities of daily life. Conclusion Despite the use of AEDs in the majority of patients, only one-third were seizure-free. Other challenges included polypharmacy, the use of valproate in women, and variable adherence. This points to a need for closer follow-up in patients with JME.

Doparesponsiv dystoni er en gruppe sykdommer som gir endrede nivåer av nevrotransmittere. Dette kan behandles med god effekt. Økt innsikt i patofysiologiske årsaksforhold har bedret forståelsen av sykdommene.Artikkelen bygger på 39 artikler fra et systematisk søk i databasen Medline, to nettsteder og en lærebok.Doparesponsiv dystoni debuterer som oftest i barne- eller ungdomsårene og gir motoriske, kognitive, psykiatriske og/eller autonome symptomer og funn. Disse kan være uspesifikke og lett mistolkes som annen nevrologisk sykdom. Sykdommen skyldes feilkoding i ett enkelt gen og arves autosomalt recessivt eller dominant. Sykdomsgivende varianter er beskrevet fra tre ulike gener: guanosintrifosfat (GTP)-syklohydrolase-1-genet, sepiapterinreduktase-genet og tyrosinhydroksylase-genet. De sykdomsgivende variantene fører til enzymdefekt og gir tidlig debuterende dystoni, som responderer godt på levodopa. Nivåbestemmelse av pteriner, biogene monoaminer og deres metabolitter i spinalvæsken samt genetiske undersøkelser gir den eksakte diagnosen.Dagens kunnskap baserer seg på kasuistikker og mindre pasientmaterialer. Her fremgår det at pasientgruppen har stor nytte av levodopa. Diagnostikken har blitt enklere de siste årene med nyere biokjemiske og molekylærgenetiske analysemetoder. Basert på dagens litteratur er det grunn til å tro at vi har udiagnostiserte pasienter i Norge med doparesponsiv dystoni.

SummaryObjective Despite juvenile myoclonic epilepsy (JME) being considered one of the most common epilepsies, population-based prevalence studies of JME are lacking. Our aim was to estimate the prevalence of JME in a Norwegian county, using updated diagnostic criteria. Methods This was a cross-sectional study, based on reviews of the medical records of all patients with a diagnosis of epilepsy at Drammen Hospital in the period 1999–2013. The study population consisted of 98,152 people

A healthy 26-year-old man with cerebral arteriovenous malformation underwent staged endovascular embolization with Onyx followed by awake craniotomy for resection. The perioperative course was complicated by tachycardia and severe intraoperative hypoxemia requiring significant oxygen supplementation. Postoperative chest computed tomography (CT) revealed hyperattenuating Onyx embolization material within the pulmonary vasculature, and an electrocardiogram indicated possible right heart strain, supporting clinically significant embolism. With awake arteriovenous malformation resection following adjunctive Onyx embolization becoming increasingly employed for lesions involving the eloquent cortex, anesthesiologists need to be aware of pulmonary migration of Onyx material as a potential contributor to significant perioperative hypoxemia.

Background Juvenile myoclonic epilepsy (JME) is a common subtype of genetic generalized epilepsy (GGE) arising in adolescence and is often associated with executive function (EF) deficits. Some EF components like response inhibition have been extensively evaluated in JME, but few studies have focused upon trait impulsivity or compared between GGE subtypes. The aim of the present study was to compare the association of trait impulsivity in JME with other GGE subtypes. Methods Patients with GGE aged between 14 and 40 years (n = 137) were divided into those with JME (n = 92) and those with other GGEs (n = 45: 8 childhood absence epilepsy (CAE), 22 juvenile absence epilepsy (JAE), and 15 epilepsy with generalized tonic–clonic seizures only (EGTCS)). The study participants were recruited through medical records of the general population of Buskerud County and the neighboring municipalities, covering 477,000 people or 9.1% of Norway's total population. All participants underwent a clinical interview including the Barratt Impulsiveness Scale (BIS), an established measure of trait impulsivity. We controlled for other potential predictors of BIS score using analysis of covariance (ANCOVA). Results There were no differences between JME and other types of GGE for BIS scores, but the presence of myoclonic seizures within the last year, irrespective of GGE subtype, was independently associated with significantly increased behavioral impulsivity. Conclusions This study demonstrates that trait impulsivity in GGE is most strongly related to the recent occurrence of myoclonic seizures rather than GGE subtype.

A 65-year-old man undergoing posterior cervical decompression and fusion demonstrated absent lower extremity evoked potential (EP) after prone positioning and before incision. Localized EP change pointed to either a technical or positional culprit. After excluding technical causes, we performed a wake-up test to rule out positioning as the culprit. During the test, we observed both symmetrical and asymmetrical hemispheric changes in density spectral array β and γ bands that correlated with awakening, eye-opening, and extremity movements. By providing real-time information on brain state, processed electroencephalogram (EEG) can facilitate a safe wake-up test by showing high-power β and γ activities that precede awakening.

Objectives Withdrawal of antiepileptic drugs (AEDs) has been discouraged in juvenile myoclonic epilepsy (JME). However, impulsivity as a consequence of executive dysfunction in JME may influence treatment adherence. The aim of the present study was to assess how common withdrawal of AEDs is in a large and representative JME group. Materials and methods Patients with genetic generalized epilepsy (GGE) were identified through a retrospective search of medical records at Drammen Hospital, Norway, and invited to a clinical interview. Information related to AED withdrawal was analyzed in those classified as JME. Results A total of 132 patients with GGE were interviewed (87 JME). Thirty-five patients with JME (40%) discontinued AEDs, of which 74% did so without consulting a doctor. The rate of self-withdrawal was significantly higher in JME than in other types of GGE. Having a parent with psychosocial difficulties was significantly over-represented in the JME self-withdrawal group. Twelve of those who discontinued AEDs (34%) were free from generalized tonic-clonic seizures (GTCS) and without antiepileptic drugs >1 year. All but one of them withdrew AEDs without consulting a doctor. Age at first motor seizure was significantly higher in those with a favorable outcome of AED withdrawal. Conclusions Self-withdrawal of AEDs is common in JME, especially in those with troublesome conditions at home. However, about 1/3 may remain free from GTCS without AEDs. The findings indicate a need for a stronger follow-up with appropriate information about the prognosis of the disorder.

Objectives A family with homocarnosinosis was reported in the literature in 1976. Three affected siblings had spastic paraplegia, retinitis pigmentosa, mental retardation, and cerebrospinal fluid (CSF) homocarnosine concentrations 20 times higher than in controls. Based on the clinical findings and new genetic techniques, we have been able to establish a precise genetic diagnosis. Method The medical records were re-evaluated, and genetic analyses were performed post-mortem in this original family. SNP array-based whole genome homozygosity mapping and Sanger sequencing of the SPG11 gene were performed. Seven additional Norwegian SPG11 patients and their disease-causing variants and clinical findings were evaluated. Homocarnosine levels in CSF were measured in four of these seven patients. Results A homozygous pathogenic splice-site variant in the SPG11 gene, c.2316 + 1G>A, was found. The clinical findings in the original family correlate with the heterogeneous SPG11 phenotype. The same variant was found in seven other Norwegian SPG11 patients, unrelated to the original family, either as homozygous or compound heterozygous constellation. Normal homocarnosine levels were found in the CSF of all unrelated SPG11 patients. Conclusions A re-evaluation of the clinical symptoms and findings in the original family correlates with the SPG11 phenotype. The increased levels of homocarnosine do not seem to be a biomarker for SPG11 in our patients. Homocarnosinosis is still a biochemical aberration with unknown clinical significance.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a hereditary neurodegenerative disorder caused by a mutation on the X chromosome. The major signs and symptoms are tremor, ataxia and parkinsonism. Up to one in 2 000 persons over 50 years of age will develop the syndrome. There is reason to believe that too few individuals in Norway undergo testing for this condition.

Background: Oculogyric crises are involuntary movements of the eyeballs and can occur due to different etiologies. Phenomenology Shown: This video abstract shows a man with oculogyric crises due to side effect of neuroleptics. Educational Value: Oculogyric crises are easy to recognize if once seen., Tremor and Other Hyperkinetic Movements, Tremor and Other Hyperkinetic Movements

International audience; OBJECTIVE: Differential diagnosis of autosomal recessive cerebellar ataxias can be challenging. A ranking algorithm named RADIAL that predicts the molecular diagnosis based on the clinical phenotype of a patient has been developed to guide genetic testing and to align genetic findings with the clinical context. METHODS: An algorithm that follows clinical practice, including patient history, clinical, magnetic resonance imaging, electromyography, and biomarker features, was developed following a review of the literature on 67 autosomal recessive cerebellar ataxias and personal clinical experience. Frequency and specificity of each feature were defined for each autosomal recessive cerebellar ataxia, and corresponding prediction scores were assigned. Clinical and paraclinical features of patients are entered into the algorithm, and a patient's total score for each autosomal recessive cerebellar ataxia is calculated, producing a ranking of possible diagnoses. Sensitivity and specificity of the algorithm were assessed by blinded analysis of a multinational cohort of 834 patients with molecularly confirmed autosomal recessive cerebellar ataxia. The performance of the algorithm was assessed versus a blinded panel of autosomal recessive cerebellar ataxia experts. RESULTS: The correct diagnosis was ranked within the top 3 highest-scoring diagnoses at a sensitivity and specificity of \textgreater90% for 84% and 91% of the evaluated genes, respectively. Mean sensitivity and specificity of the top 3 highest-scoring diagnoses were 92% and 95%, respectively. The algorithm outperformed the panel of ataxia experts (p = 0.001). INTERPRETATION: Our algorithm is highly sensitive and specific, accurately predicting the underlying molecular diagnoses of autosomal recessive cerebellar ataxias, thereby guiding targeted sequencing or facilitating interpretation of next-generation sequencing data. Ann Neurol 2017;82:892-899.

Objective Although a significant amount of experience has accumulated for awake procedures for brain tumor, epilepsy, and carotid surgery, its utility for intracranial neurovascular indications remains largely undefined. Awake surgery for select neurovascular cases offers the advantage of precise brain mapping and robust neurologic monitoring during surgery for lesions in eloquent areas, avoidance of potential hemodynamic instability, and possible faster recovery. It also opens the window for perilesional epileptogenic tissue resection with potentially less risk for iatrogenic injury. Methods Institutional review board approval was obtained for a retrospective review of awake surgeries for intracranial neurovascular indications over the past 36 months from a prospectively maintained quality database. We reviewed patients' clinical indications, clinical and imaging parameters, and postoperative outcomes. Results Eight consecutive patients underwent 9 intracranial neurovascular awake procedures conducted by the senior author. A standardized “sedated–awake–sedated” protocol was used in all 8 patients. For the 2 patients with arteriovenous malformations and the 3 patients with cavernoma, awake brain surface and white matter mapping was performed before and during microsurgical resection. A neurological examination was obtained periodically throughout all 5 procedures. There were no intraoperative or perioperative complications. Hypotension was avoided during the 2 Moyamoya revascularization procedures in the patient with a history of labile blood pressure. Postoperative imaging confirmed complete arteriovenous malformation and cavernoma resections. No new neurologic deficits or new-onset seizures were noted on 3-month follow-up. Conclusions Awake surgery appears to be safe for select patients with intracranial neurovascular pathologies. Potential advantages include greater safety, shorter length of stay, and reduced cost.

In some cases of cerebral aneurysm clipping, direct clip application to the aneurysm neck may be difficult or the aneurysm may rupture unexpectedly. In these cases, a clip may be temporarily applied to the parent artery to reduce aneurysmal wall tension, facilitate permanent clip placement, or control bleeding if the aneurysm ruptures. In certain circumstances, even applying a temporary clip may be challenging. We present a case in which the aneurysm ruptured and IV administration of adenosine was required to facilitate clipping. This case suggests that administering multiple consecutive precalculated doses of adenosine may be a safe method to manage aneurysmal rupture.

Background: Surgery for posterior spine instrumentation often requires major transfusion. The aim of this study was to develop and test the validity of a model for predicting intraoperative major transfusion (>4 U total red blood cells), based on preoperative patient and surgical variables, that was applicable to adult patients undergoing cervical, thoracic, and/or lumbar spine deformity surgery with and without osteotomies. Materials and Methods: The perioperative data from 548 patients who underwent ≥3 levels of posterior spinal fusion with instrumentation between January 1, 2003 and May 30, 2009, were retrospectively collected to create a model for predicting major blood transfusion. The validity of the model was retrospectively tested with a separate data set of 95 patients who underwent surgery from June 1, 2009 through September 30, 2010. Results: There was a 59.5% incidence of major transfusion in the derivation set of patients. Independent predictors of major transfusion were operation duration, number of posterior levels instrumented, surgical complexity score, and preincision hemoglobin. This model was able to predict major transfusion significantly better than a previously published model (ROCAUC=0.89; 99% confidence interval, 0.80-0.90; P Conclusions: Our model has an increased accuracy for predicting the probability of major transfusion compared with a previously published model. In addition, our model is applicable to all types of spine fusion surgery and accounts for the complexity of surgical instrumentation, the number of levels instrumented, and the predicted duration of surgery as independent variables.

Total intravenous anesthesia (TIVA) with propofol and opioids is frequently utilized for spinal surgery when somatosensory evoked potentials (SSEPs) and transcranial motor evoked potentials (tcMEPs) are monitored. Many anesthesiologists would prefer to utilize low dose halogenated anesthetics (e.g. 1/2 MAC). We examined our recent experience using 3 % desflurane or TIVA during spine surgery to determine the impact on propofol usage and on the evoked potential responses. After institutional review board approval we conducted a retrospective review of a 6 month period for adult spine patients who were monitored with SSEPs and tcMEPs. Cases were included for the study if anesthesia was conducted with propofol–opioid TIVA or 3 % desflurane supplemented with propofol or opioid infusions as needed. We evaluated the propofol infusion rate, cortical amplitudes of the SSEPs (median nerve, posterior tibial nerve), amplitudes and stimulation voltage for eliciting the tcMEPs (adductor pollicis brevis, tibialis anterior) and the amplitude variability of the SSEP and tcMEP responses as assessed by the average percentage trial to trial change. Of the 156 spine cases included in the study, 95 had TIVA with propofol–opioid (TIVA) and 61 had 3 % expired desflurane (INHAL). Three INHAL cases were excluded because the desflurane was eliminated because of inadequate responses and 26 cases (16 TIVA and 10 INHAL) were excluded due to significant changes during monitoring. Propofol infusion rates in the INHAL group were reduced from the TIVA group (average 115–45 μg/kg/min) (p

OBJECTIVES: Sepiapterin reductase deficiency is a rare, but treatable inherited disorder of tetrahydrobiopterin and neurotransmitter metabolism. This disorder is most probably underdiagnosed. To date, only 44 cases have been described in the literature. We present the clinical and genetic investigations in a family with a complex movement disorder. MATERIALS AND METHODS: We examined two affected sisters and three healthy family members. The cerebrospinal fluid was analyzed for neurotransmitter and pterins, and the sepiapterin reductase gene (SPR) was sequenced. RESULTS: The sisters had a complex movement disorders with dystonia and diurnal fluctuations. Both had oculogyric crises, and the older sister also hypersomnia. Both sisters had raised prolactin levels twice above the reference level. One sister had a dramatic response to levodopa, the other responded, but developed dyskinesia despite low doses. Both patients improved dramatically over time with levodopa (2.3 and 1.5 mg/kg/day). Very low levels of homovanillic acid and 5-hydroxyindoleacetic acid and increased levels of sepiapterin and dihydrobiopterin were measured in the cerebrospinal fluid before treatment. DNA analyses revealed a novel homozygous mutation in exon 2 in the SPR gene, c.364A>G/p.(Tyr123Cys), located in a highly conserved region in the gene. Both parents and the healthy sister were carriers for the same mutation. CONCLUSIONS: A new homozygous mutation in the SPR gene was found in two sisters with dopa-responsive dystonia. This important and treatable neurotransmitter disorder must be considered in patients with a complex movement disorder with diurnal fluctuations with or without intellectual impairment. Patients with these symptoms should undergo levodopa trial, cerebrospinal fluid investigations, and genetic analyses.

Arteriovenous malformations (AVMs) of the brain are very complex and intriguing pathologies. Since their initial description by Luschka and Virchow in the middle of the 19th century, multiple advances and innovations have revolutionized their management and surgical treatment. Here, we review the historical landmarks in the surgical treatment of AVMs and then illustrate the most recent and futuristic technologies aiming to improve outcomes in AVM surgeries. In particular, we examine potential advances in patient selection, imaging, surgical technique, neuroanesthesia, and postoperative neuro-rehabilitation and quantitative assessments. Finally, we illustrate how concurrent advances in radiosurgery and endovascular techniques might present new opportunities to treat AVMs more safely from a surgical perspective.

Despite extensive efforts, half of patients with rare movement disorders such as hereditary spastic paraplegias and cerebellar ataxias remain genetically unexplained, implicating novel genes and unrecognized mutations in known genes. Non-coding DNA variants are suspected to account for a substantial part of undiscovered causes of rare diseases. Here we identified mutations located deep in introns of POLR3A to be a frequent cause of hereditary spastic paraplegia and cerebellar ataxia. First, whole-exome sequencing findings in a recessive spastic ataxia family turned our attention to intronic variants in POLR3A, a gene previously associated with hypomyelinating leukodystrophy type 7. Next, we screened a cohort of hereditary spastic paraplegia and cerebellar ataxia cases (n = 618) for mutations in POLR3A and identified compound heterozygous POLR3A mutations in ∼3.1% of index cases. Interestingly,80% of POLR3A mutation carriers presented the same deep-intronic mutation (c.1909+22GA), which activates a cryptic splice site in a tissue and stage of development-specific manner and leads to a novel distinct and uniform phenotype. The phenotype is characterized by adolescent-onset progressive spastic ataxia with frequent occurrence of tremor, involvement of the central sensory tracts and dental problems (hypodontia, early onset of severe and aggressive periodontal disease). Instead of the typical hypomyelination magnetic resonance imaging pattern associated with classical POLR3A mutations, cases carrying c.1909+22GA demonstrated hyperintensities along the superior cerebellar peduncles. These hyperintensities may represent the structural correlate to the cerebellar symptoms observed in these patients. The associated c.1909+22GA variant was significantly enriched in 1139 cases with spastic ataxia-related phenotypes as compared to unrelated neurological and non-neurological phenotypes and healthy controls (P = 1.3 × 10-4). In this study we demonstrate that (i) autosomal-recessive mutations in POLR3A are a frequent cause of hereditary spastic ataxias, accounting for about 3% of hitherto genetically unclassified autosomal recessive and sporadic cases; and (ii) hypomyelination is frequently absent in POLR3A-related syndromes, especially when intronic mutations are present, and thus can no longer be considered as the unifying feature of POLR3A disease. Furthermore, our results demonstrate that substantial progress in revealing the causes of Mendelian diseases can be made by exploring the non-coding sequences of the human genome.

When temporary arterial occlusion of the parent artery is difficult for anatomical reasons, or when inadvertent aneurysmal rupture occurs during surgical dissection, adenosine administration can be used to produce flow arrest and brief, profound systemic hypotension that can facilitate intracranial aneurysm clip ligation. There is a concern, however, that the flow arrest and profound hypotension produced by adenosine, although brief, may cause cerebral ischemia and therefore worsen neurologic outcome compared with other techniques to facilitate aneurysm clip ligation. Therefore, we performed a retrospective, case-control study to determine whether adenosine-induced flow arrest had negative effects on the neurologic outcome of our patients.We reviewed the perioperative records of all patients in our intracranial aneurysm surgery outcomes database between August 1, 2006, and June 15, 2012. The primary outcome was the presence or absence of a poor neurologic outcome 48 hours after surgery, with a modified Rankin scale score2 being defined as a poor neurologic outcome. The neurologic outcome at the time of hospital discharge was a secondary outcome. Secondary outcomes related to cardiac morbidity included atrial or ventricular arrhythmia requiring treatment and elevated cardiac biomarkers consistent with ischemia (i.e., Troponin-I).During the study period, adenosine-induced flow arrest was used in 72 of the 413 patients (17.4%) who underwent intracranial aneurysm clip ligation. The difference in the incidence of poor neurological outcome, with or without the use of adenosine, was no larger than 15.7% at 48 hours after surgery (P =0.524) or -12.7% at discharge (P = 0.741). In addition, the difference in the incidence of cardiac morbidity was no larger than -16.0% for persistent arrhythmia (P = 0.155) or -9.4% for biomarkers of myocardial ischemia (P = 0.898) in the initial 48 hours after surgery.When used to facilitate intracranial aneurysm clip ligation, adenosine-induced flow arrest was associated with no more than a 15.7% increase or a 12.7% decrease in the incidence of a poor neurologic outcome at either 48 hours or at the time of hospital discharge. In addition, adenosine use was not associated with cardiac morbidity in the perioperative period (i.e., persistent arrhythmia or biomarkers of cardiac ischemia).

Total intravenous anesthesia (TIVA) with propofol and opioids is frequently utilized for spinal surgery where somatosensory evoked potentials (SSEP) and motor evoked potentials (tcMEP) are monitored. Lidocaine infusions can contribute to antinociception and unconsciousness, thus allowing for a reduction in the total dose of propofol. We examined our recent experience with lidocaine infusions to quantify this effect. After institutional review board approval, we conducted a retrospective review of propofol usage in propofol-opioid TIVA (with and without lidocaine) for spine cases monitored with SSEP and tcMEP over a 7 months period. The propofol infusion rate, cortical amplitudes of the SSEP (median nerve, posterior tibial nerve), amplitudes and stimulation voltage of the tcMEP (adductor pollicis brevis, tibialis anterior) were evaluated. The savings of propofol and sufentanil were estimated based on utilization in 50 milliliter (ml) bottles and 5 ml ampules, respectively. 129 cases were evaluated. Propofol infusion rates were reduced with lidocaine infusion from an average of 115-99 μg/kg/min (p = 0.00038) and sufentanil infusions from an average of 0.36-0.29 μg/kg/h (p = 0.0059). This reduction in propofol infusion was also seen when the cases were divided into anterior cervical, posterior cervical, or posterior thoraco-lumbar procedures. No significant differences in the cortical SSEP or tcMEP amplitudes or the tcMEP stimulation voltages used were observed. No complications were associated with the use of the lidocaine infusion. The total estimated drug savings included 104 50 ml bottles of propofol and 5 5 ml ampules of sufentanil. These cases indicate that a lidocaine infusion can be effectively utilized in spine surgery with SSEP and tcMEP monitoring as a means to reduce propofol and sufentanil usage without a negative effect on the monitoring.

Anemia is common in patients with aneurysmal subarachnoid hemorrhage (SAH), but these patients have constituted only a small fraction of those studied in large trials of anemia and transfusion. Unlike other critically ill patients, those with SAH face a well-defined risk of vasospasm and cerebral ischemia in the weeks after their hemorrhage. The risk of ongoing ischemia may make them less able to tolerate anemia and more likely to benefit from blood transfusion. The available data show that anemia is associated with poor outcomes after SAH but that blood transfusion does not consistently improve physiological markers, and it may be associated with poor outcomes. Most of these data are observational in nature, although 1 recent study demonstrated the safety and feasibility of maintaining relatively high transfusion thresholds in patients with SAH. Larger, randomized trials are needed to determine at what levels of anemia patients with SAH might benefit from transfusion, the optimal timing of transfusion, and how to identify those patients who are most likely to benefit.

Standardization and accreditation of fellowship training have been considered in the field of neuroanesthesiology. A prior survey of members of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) suggested strong support for accreditation and standardization. In response, SNACC created a Task Force that developed curricular guidelines for neuroanesthesiology fellowship training programs. These guidelines represent a first step toward standards for neuroanesthesiology training and will be useful if accreditation is pursued in the future.

BACKGROUND Mannitol is often used during intracranial surgery to improve surgical exposure. Furosemide is often added to mannitol to augment this effect. The concern exists, however, that the augmented diuresis caused by the addition of furosemide to mannitol may cause hypovolemia and hypoperfusion, hypokalemia, and hyponatremia. We examined the intraoperative safety of low-dose furosemide (0.3 mg/kg) combined with mannitol (1 g/kg). METHODS We observed 23 patients in a double-blind, block randomized, placebo-controlled study to examine the effects of furosemide (0.3 mg/kg) when combined with mannitol (1 g/kg) on surgical brain relaxation for tumor surgery. Mannitol and the study drug (furosemide or placebo) were administered, and arterial blood gases with electrolytes (sodium, potassium, and lactic acid) and urine output volume were recorded every 30 minutes for 3 hours. Plasma sodium, potassium, and lactic acid concentrations, and interval urine outputs, were compared across time and between furosemide-placebo assignment groupings, with a P

Advances in electrophysiological monitoring have improved the ability of surgeons to make decisions and minimize the risks of complications during surgery and interventional procedures when the central nervous system (CNS) is at risk. Individual techniques have become important for identifying or mapping the location and pathway of critical neural structures. These techniques are also used to monitor the progress of procedures to augment surgical and physiologic management so as to reduce the risk of CNS injury. Advances in motor evoked potentials have facilitated mapping and monitoring of the motor tracts in newer, more complex procedures.

The purpose of this study was to identify risk factors associated with intraoperative blood transfusions in patients presenting for intracranial aneurysm surgery in the current era of more restrictive transfusion guidelines.Retrospective observational cohort study with stepwise, multivariate binary logistic regression analysis.Tertiary care university teaching hospital.Four hundred seventy-one consecutive patients undergoing intracranial aneurysm surgery at Northwestern Memorial Hospital (Chicago, IL) from 2006 to 2012.Red blood cell transfusion (retrospective observational).Demographic data, medical comorbidities, hemoglobin levels, Hunt-Hess grades, intracranial aneurysm characteristics, presenting intracranial bleeding states, estimated blood losses, transfused red blood cells, and blood products.Forty-six patients (9.5%) received intraoperative red blood cell transfusions. Preoperative risk factors associated with transfusions were highly related to aneurysm rupture, including such parameters as older age (P.001), lower presenting hemoglobin level (P.001), preoperative rupture (P.001), and higher Hunt-Hess grade (P.001). Intraoperative risk factors included larger aneurysm size (10 mm; P = .03), intraventricular hemorrhage (P.001), and intracerebral hematoma evacuation (P = .02). Binary logistic regression modeling identified age (P.001), presenting hemoglobin level (P.001), larger aneurysm size (10 mm; P = .003), elevated Hunt-Hess grade (P = .021), and intraoperative rupture (P = .013) as independent predictors of intraoperative red blood cell transfusion.The incidence of intraoperative red blood cell transfusion in intracranial aneurysm surgery in our patient cohort was 9.5%, and the most significant factors associated with transfusion were presenting hemoglobin level less than 11.7 g/dL and age greater than 52 years. It would seem advisable that these patients undergo routine type and cross-matching of red blood cells before intracranial aneurysm surgery.

Background Benign hereditary chorea (BHC) is a rare autosomal dominant disorder characterised by childhood onset that tends to improve in adulthood. The associated gene, NKX2-1 (previously called TITF1 ), is essential for organogenesis of the basal ganglia, thyroid and lungs. The aim of the study was to refine the movement disorders phenotype. We also studied disease course and response to therapy in a large series of genetically proven patients. Methods We analysed clinical, genetic findings and follow-up data in 28 NKX2-1 mutated BHC patients from 13 families. Results All patients had private mutations, including seven new mutations, three previously reported mutations and three sporadic deletions encompassing the NKX2-1 gene. Hypotonia and chorea were present in early infancy, with delayed walking ability (25/28); dystonia, myoclonus and tics were often associated. Attention deficit hyperactivity disorder (ADHD) was present in seven. Among the 14 patients followed-up until adulthood, nine had persistent mild chorea, two had near total resolution of chorea but persistent disabling prominent myoclonus and three recovered completely. Learning difficulties were observed in 20/28 patients, and three had mental retardation. Various combinations of BHC, thyroid (67%) and lung (46%) features were noted. We found no genotype–phenotype correlation. A rapid and sustained beneficial effect on chorea was obtained in 5/8 patients treated with tetrabenazine. Conclusion Early onset chorea preceded by hypotonia is suggestive of BHC. Associated thyroid or respiratory disorders further support the diagnosis and call for genetic studies. Tetrabenazine may be an interesting option to treat disabling chorea.

BACKGROUND Clip application for temporary occlusion is not always practical or feasible. Adenosine is an alternative that provides brief periods of flow arrest that can be used to advantage in aneurysm surgery, but little has been published on its utility for this indication. OBJECTIVE To report our 2-year consecutive experience with 40 aneurysms in 40 patients for whom we used adenosine to achieve temporary arterial occlusion during aneurysm surgery. METHODS We retrospectively reviewed our clinical database between May 2007 and December 2009. All patients who underwent microsurgical clipping of intracranial aneurysms under adenosine-induced asystole were included. Aneurysm characteristics, reasons for adenosine use, postoperative angiographic and clinical outcome, cardiac complications, and long-term neurological follow-up with the modified Rankin Scale were noted. RESULTS Adenosine was used for 40 aneurysms (10 ruptured, 30 unruptured). The most common indications for adenosine were aneurysm softening in 17 cases and paraclinoid location in 14 cases, followed by broad neck in 12 cases and intraoperative rupture in 6 cases. Troponins were elevated postoperatively in 2 patients. Echocardiography did not show acute changes in either. Clinically insignificant cardiac arrhythmias were noted in 5 patients. Thirty-six patients were available for follow-up. Mean follow-up was 12.8 months. The modified Rankin Scale score was 0 for 29 patients at the time of the last follow-up. Four patients had an modified Rankin Scale score of 1, and scores of 2 and 3 were found in 2 and 1 patients, respectively. CONCLUSION Adenosine appears to allow safe flow arrest during intracranial aneurysm surgery. This can enhance the feasibility and safety of clipping in select circumstances.

Bradycardia caused by the oculocardiac reflex is an anticipated occurrence during certain surgeries. The afferent pathway involves the trigeminal nerve's ophthalmic division. Reflex bradycardia from the trigeminocardiac reflex, via stimulation of maxillary or mandibular divisions of cranial nerve V, although less well known, has also been reported intraoperatively. Unstable bradycardia associated with stimulation of the mandibular division of cranial nerve V during trigeminal neuralgia pain episodes in the Postanesthesia Care Unit is presented.

The purpose of this study was to examine the utility and feasibility of using alternative anterior reference leads when measuring left posterior tibial nerve somatosensory evoked potentials (SEPs). With IRB approval, 12 patients were monitored using both traditional (FPz and C4′) and alternative anterior (F3 and F4) reference leads during routine spine surgery with SEP monitoring. Recordings from the routine and novel electrode pairs were collected and analyzed. All of the SEP amplitudes measured were of similar magnitude except for that of F3–F4, which was significantly lower (P

Background - Ataxia with vitamin E deficiency (AVED) is a rare cause of hereditary ataxia in north European countries with unknown prevalence. Few cases are reported from these countries. Methods -Through a systematic population based study of hereditary ataxia in southeast Norway subjects were classified and investigated. Aims - To report a subject with ataxia due to vitamin E deficiency in Norway. Results - One patient with AVED was identified. The subject was a 45 years old woman with progressive ataxia from preschool age. When she was 12 years old Friedreich's ataxia was diagnosed after neurological examination. At the age of 45 re-evaluation and re-examination was performed and genetic analysis of the Frataxin gene was negative. At that time she had truncal and extremities ataxia, titubation of the head, pes cavus, inverted plantar response, loss of proprioceptive and vibration sense and a severe sensory neuropathy. Vitamin E in serum was undetectable and genetic analysis detected a compound heterozygous mutation, p.A120T and p.R134X, in the α-tocopherol transport protein gene on chromosome 8q13. Discussion - Vitamin E should always be assessed in progressive ataxia of genetic or unexplained causes and especially with a Friedreich's ataxia-like phenotype since treatment is available. Conclusion - AVED is rare in Norway, but exists, and we here report the first genetically confirmed subject with ataxia due to vitamin E deficiency in Norway.

Introduction - The relative frequencies of different ataxias vary among different ethnic and geographic groups. The aim of this study was to examine patients with cerebellar ataxia and find the occurrence of autosomal dominant and recessive cerebellar ataxias in the population of the southern and eastern parts of Norway and estimate its prevalence. Materials and methods - Probands were systematically tested for spinocerebellar ataxia 1, 2, 3, 6 and Friedreich's ataxia. A total of 94 patients with ataxia were assessed. Results - We registered 60 patients from 39 unrelated families with hereditary ataxias. One family with SCA2 (two patients), one family with Friedreich's ataxia (two patients), two patients heterozygote for Friedreich's ataxia and one metabolic ataxia were identified. Conclusions - We have few Friedreich's ataxia and SCA 1,2,3 and 6 in our population. Prevalence in Oslo County was estimated at 2.2/100,000 for autosomal recessive and 3.0/100,000 for autosomal dominant ataxia, respectively.

Updated knowledge on the prevalence of epilepsy is valuable for planning of health services to this large and complex patient group. Comprehensive epidemiological research on epilepsy has been undertaken, but because of variations in methodology, the results are difficult to compare. The objective of this article is to present evidence-based estimates of the prevalence and incidence of epilepsy in the Nordic countries.The article is based on a search in PubMed with the search terms epilepsy and epidemiology, combined with each of the Nordic countries separately.Altogether 38 original articles reported incidence and/or prevalence rates of epilepsy in a Nordic country. Four studies had investigated the prevalence of active epilepsy in all age groups, with results ranging from 3.4 to 7.6 per 1,000 inhabitants. Only two studies had investigated the incidence of epilepsy in a prospective material that included all age groups. The reported incidence amounted to 33 and 34 per 100,000 person-years respectively. A prospective study that only included adults reported an incidence of 56 per 100,000 person-years.We estimate that approximately 0.6% of the population of the Nordic countries have active epilepsy, i.e. approximately 30,000 persons in Norway. Epilepsy is thus one of the most common neurological disorders. The incidence data are more uncertain, but we may reasonably assume that 30-60 new cases occur per 100,000 person-years.

Background and purpose SPG7 is one of the most common forms of autosomal recessive hereditary spastic paraplegia. The phenotype has been shown to be heterogeneous, varying from a complex spastic ataxia to pure spastic paraplegia or pure ataxia. The aim of this study was to clinically and genetically characterize patients with SPG7 in Norway. Methods Six Norwegian families with a clinical diagnosis of hereditary spastic paraplegia were diagnosed with SPG7 through Sanger sequencing and whole-exome sequencing. Haplotypes were established to identify a possible founder mutation. All patients were thoroughly examined and the clinical and molecular findings are described. Results The core phenotype was spastic paraparesis with ataxia, bladder disturbances and progressive external ophthalmoplegia. The variant p.H701P was identified in homozygous state in one family and in compound heterozygous state in three families. Haplotype analysis of seven surrounding single nucleotide polymorphisms supports that this variant resides on a founder haplotype. Four of the families were compound heterozygous for the previously well-described p.A510V variant. Conclusion SPG7 is a common subgroup of hereditary spinocerebellar disorders in Norway. The broad phenotype in the Norwegian SPG7 population illustrates the challenges with the traditional dichotomous classification of hereditary spinocerebellar disorders into hereditary spastic paraplegia or hereditary ataxia. A Norwegian founder mutation p.H701P was identified in four out of six families, making it a major cause of SPG7 in Norway.

SummaryObjective Epilepsy represents a substantial personal and social burden worldwide. When addressing the multifaceted issues of epilepsy care, updated epidemiologic studies using recent guidelines are essential. The aim of this study was to find the prevalence and causes of epilepsy in a representative Norwegian county, implementing the new guidelines and terminology suggested by the International League Against Epilepsy (ILAE). Methods Included in the study were all patients from Buskerud County in Norway with a diagnosis of epilepsy at Drammen Hospital and the National Center for Epilepsy at Oslo University Hospital. The study period was 1999–2014. Patients with active epilepsy were identified through a systematic review of medical records, containing information about case history, electroencephalography (EEG), cerebral magnetic resonance imaging (MRI), genetic tests, blood samples, treatment, and other investigations. Epilepsies were classified according to the revised terminology suggested by the ILAE in 2010. Results In a population of 272,228 inhabitants, 1,771 persons had active epilepsy. Point prevalence on January 1, 2014 was 0.65%. Of the subjects registered with a diagnostic code of epilepsy, 20% did not fulfill the ILAE criteria of the diagnosis. Epilepsy etiology was structural-metabolic in 43%, genetic/presumed genetic in 20%, and unknown in 32%. Due to lack of information, etiology could not be determined in 4%. Significance Epilepsy is a common disorder, affecting 0.65% of the subjects in this cohort. Every fifth subject registered with a diagnosis of epilepsy was misdiagnosed. In those with a reliable epilepsy diagnosis, every third patient had an unknown etiology. Future advances in genetic research will probably lead to an increased identification of genetic and hopefully treatable causes of epilepsy.