Choreiform movements and basal ganglia calcification as a presentation of Fahr's disease

Basal ganglia calcifications may be a radiological finding in approximately 20% of the general population. When they are associated with neuropsychiatric and motor symptoms in an idiopathic form, they are known as Fahr's disease. They are termed "Fahr's syndrome" when they are secondary to an identifiable and potentially treatable cause. In this report, we present the clinical case of a 69-year-old woman with the onset of subacute chorea, with no other associated symptoms, in whom extensive basal ganglia calcifications were found on neuroimaging, due to which metabolic disorders were subsequently ruled out. The objective is to contribute to the characterization of the potential motor manifestations which would give rise to clinical suspicion. Due to its low incidence and the little information on this condition in the region, we want to encourage documentation of other cases and the process for ruling out other differential diagnoses, in order to obtain more information on its actual epidemiology and signs and symptoms in Colombia. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2635).

Uso del cannabis medicinal en niños con encefalopatías epilépticas farmacorresistentes. Experiencia en Hospital Garrahan / Use of medicinal cannabis in children with drug-resistant epileptic encephalopathies. Experience at Garrahan Hospital

Objetivo: Reportamos resultados sobre la efectividad, seguridad y tolerancia del cannabidiol como adyuvante terapéutico en pacientes pediátricos con encefalopatías epilépticas del desarrollo (EED) resistentes al tratamiento farmacológico y no farmacológico tras un seguimiento promedio de 20 meses. Métodos: Se realizó un estudio de cohorte prospectivo para evaluar la eficacia, la seguridad y la tolerancia del aceite de cannabis medicinal enriquecido con CBD añadido a los medicamentos anticonvulsivos estándar en niños con EED resistentes a los medicamentos atendidos en un único centro. Resultados: Entre octubre de 2018 y marzo de 2020, se incluyeron 59 pacientes. La edad media en el momento del inicio del protocolo fue de 10,5 años (rango, 2-17 años). La mediana de la duración del tratamiento fue de 20 meses (rango, 12-32). La mediana de edad en el momento de la primera convulsión fue de 8 meses (rango, 1 día - 10 años). Al final del seguimiento, el 78% de los niños tenía una disminución ≥ 50% en frecuencia de las crisis y el 47,5% tenía una disminución > 75%. Siete pacientes (11,9%) estaban libres de convulsiones. El número de crisis se redujo de una mediana de 305/mes a 90/mes, que supone una reducción media del 57% y una mediana del 71% (p < 0,0001). Los efectos adversos fueron en su mayoría leves o moderados. El CBD se interrumpió en 17 pacientes (28,8%) por falta de respuesta al tratamiento, aumento de la frecuencia de las convulsiones, intolerancia al fármaco o cumplimiento terapéutico insuficiente. Conclusión: En los niños con EED resistentes a los fármacos, el tratamiento a largo plazo del cannabis medicinal enriquecido con CBD como terapia adyuvante resultó ser seguro, bien tolerado y eficaz. Las reducciones sostenidas en la frecuencia de las convulsiones y la mejora de los aspectos de la vida diaria se observaron en comparación con nuestros preliminares (AU)

Objective: We report results on the effectiveness, safety, and tolerance of cannabidiol (CBD) as add-on therapy in children with developmental and epileptic encephalopathies (DEE) resistant to pharmacological and non-pharmacological treatment after a mean follow-up of 20 months. Methods: A prospective cohort study was conducted to evaluate the efficacy, safety, and tolerability of CBD-enriched medical cannabis oil added to standard antiseizure medications in children with drug-resistant DEEs seen at a single center. Results: Between October 2018 and March 2020, 59 patients were included. The median age at protocol initiation was 10.5 years (range, 2-17 years). Median treatment duration was 20 months (range, 12-32). The median age at the time of the first seizure was 8 months (range, 1 day - 10 years). At the end of follow-up, 78% of the children had a decrease ≥ 50% in seizure frequency and 47.5% had a decrease of > 75%. Seven patients (11.9%) were seizure free. The number of seizures was reduced from a median of 305/month to 90/month, accounting for a mean reduction of 57% and a median of 71% (p < 0.0001). Adverse effects were mostly mild or moderate. CBD was discontinued in 17 patients (28.8%) due to lack of response to treatment, increased seizure frequency, drug intolerance, or poor compliance. Conclusion: In children with drug-resistant DEE, long-term treatment with CBD-enriched medicinal cannabis as add-on therapy proved to be safe, well tolerated, and effective. Sustained reductions in seizure frequency and improvement in aspects of daily living were observed compared to our preliminary results (AU)

Vagus Nerve Stimulation in the Treatment of Dravet Syndrome / 罕见病研究

Dravet syndrome is a epileptic syndrome characterized by drug-resistant epilepsy occuring at childhood. It is often accompanied by status epilepticus and cognitive and language impairment appearing gradually as the disease progresses. The effect of antiepileptic drugs and resection epilepsy surgery on Dravet syndrome is poor although neuromodulation surgery, especially vagus nerve stimulation, is an effective and feasible treatment for Dravet syndrome. In this article we reported a case of Dravet syndrome treated with vagus nerve stimulation, relevant literature was reviewed and summarized at the same time. A total of 141 cases of Dravet treated by vagus nerve stimulation were collected, and the overall effective rate was 53.9%.

Terapéutica de la encefalopatía posterior reversible: una revisión sistemática

RESUMEN Introducción: Síndrome de encefalopatía posterior reversible PRES (también conocido como síndrome de leucoencefalopatía posterior reversible) se presenta con síntomas de inicio rápido como cefalea, convulsiones, alteración de la conciencia y alteración visual. A menudo, pero de ninguna manera siempre, se asocia con la hipertensión aguda. Metodología: Estudio de tipo revisión sistemática de la literatura. Se realizó una revisión sistemática de la literatura en las bases de datos PubMed/MEDLINE, LILACS y CICCO utilizando la sintaxis "Posterior reversible encephalopathy syndrome AND treatment". Los límites de búsqueda fueron publicaciones hechas en los últimos cinco años (2013-2020). Resultados: Se evaluaron 235 textos completos de los cuales finalmente se seleccionaron seis, esto teniendo en cuenta que los demás artículos no mencionaban de forma explícita el tratamiento, o eran redundantes con respecto a otros ya incluidos, teniendo en cuenta que el PRES tiene un manejo sintomático más que un tratamiento específico. Discusión: Síndrome de Encefalopatía Posterior Reversible (PRES) no tiene un tratamiento específico, sino más bien tiene un tratamiento sintomático lo que hace fundamental conocer las causas subyacentes al PRES ya que esa es la terapéutica a seguir, brindar el mejor tratamiento para lo que está causando este síndrome, de allí la importancia de conocer a fondo la etiología.

ABSTRACT Introduction: Posterior reversible encephalopathy syndrome PRES (also known as posterior reversible leukoencephalopathy syndrome) presents with rapid-onset symptoms such as headache, seizures, altered consciousness, and visual impairment. Often, but by no means always, it is associated with acute hypertension. Methods: Systematic literature review type study. A systematic review of the literature was carried out in the PubMed / MEDLINE, LILACS and CICCO databases using the syntax "Posterior reversible encephalopathy syndrome AND treatment". The search limits were publications made in the last five years (2013-2020). Results: 235 full texts were evaluated, of which six were finally selected, taking into account that the other articles did not explicitly mention the treatment, or were redundant with respect to others already included, taking into account that the PRES has symptomatic rather than specific treatment. Discussion: Posterior Reversible Encephalopathy Syndrome (PRES) does not have a specific treatment, but rather has a symptomatic treatment, which makes it essential to know the underlying causes of PRES since that is the therapy to follow, to provide the best treatment for what is causing this syndrome, hence the importance of fully understanding the etiology.

Creutzfeldt-Jakob disease: one hundred years of participation in the design of the transmissible spongiform encephalopathies / Doença de Creutzfeldt-Jakob: cem anos de participação no desenho das encefalopatias espongiformes transmissíveis

Creutzfeldt and Jakob's disease (CJD) has its initial milestone in the publication issued 100 years ago that precipitated its better clinical-pathological and etiological understanding. Now, it is established that it belongs to the group of the prion diseases or transmissible spongiform encephalopathies family. CJD is itself divided into several types, the most common being sporadic that is further subdivided according to the anatomoclinical expression, but mainly due to its aetiology regarding prionic protein or genotype.

A doença de Creutzfeldt e Jakob (CJD) tem seu marco inicial na publicação emitida há 100 anos que precipitou seu melhor entendimento clínico- patológico e etiológico. Agora, está estabelecido que pertence ao grupo da família das doenças de príons ou encefalopatias espongiformes transmissíveis. A própria CJD se divide em vários tipos, sendo o mais comum o esporádico que também se subdivide de acordo com a expressão anatomoclínica, mas principalmente devido à sua etiologia em relação à proteína priônica ou genótipo.

Presence of generalized periodic discharges and hospital mortality / Presença de descargas periódicas generalizadas e mortalidade hospitalar

ABSTRACT Background: Generalized periodic discharges (GPDs) are rare patterns that can be found in long-term electroencephalographic monitoring in critical patients. These patterns have been correlated with non-seizure crisis and non-convulsive status epilepticus, associated with poor prognosis. Objective: To compare the outcome between patients who developed GPDs and patients with other abnormalities in long-term electroencephalographic monitoring. Methods: A retrospective study was performed by analyzing the medical records of 112 patients over 18 years who developed GPDs during long-term electroencephalographic monitoring (12‒16 hours of monitoring) in the intensive care unit of a general hospital, compared with a group that had only nonspecific abnormalities in the monitoring. Results: Age and cardiorespiratory arrest (CA) were risk factors for death - OR 1.04 (95% CI 1,02 - 1,07) and p<0.001; OR 3.00 (95% CI 1,01 - 8,92) and p=0.046, respectively. It was not possible to evaluate if GPDs alone were associated with an unfavorable outcome or would be a bias for the development of CA in these patients. However, of the six isolated GPDs cases, 2/3 evolved to death, showing a tendency to worse prognosis. A significant difference (p=0.031) was observed for a worse outcome when comparing the group of 28 patients who presented GPD or CA with the other group which did not present any of these variables; of these 28 patients, 20 (71.4%) died. Conclusions: The presence of post-CA GPDs was associated with worse prognosis, but it was not clear whether these patterns are independent factors of an unfavorable evolution.

RESUMO Introdução: As descargas periódicas generalizadas (DPG) são padrões raros que podem ser encontrados durante monitorização eletroencefalográfica prolongada (MEP) em pacientes críticos. Esses padrões têm sido correlacionados com crises não convulsivas e estado de mal epiléptico não convulsivo, associados a um pior prognóstico. Objetivo: Comparar o desfecho entre pacientes que desenvolveram DPG e pacientes com anormalidades inespecíficas na MEP. Métodos: Foi realizado um estudo retrospectivo através da análise dos prontuários de 112 pacientes acima de 18 anos que desenvolveram DPG durante MEP (de 12‒16 horas de monitorização) na unidade de terapia intensiva de um hospital geral, comparando com um grupo que apresentou apenas anormalidades inespecíficas na MEP. Resultados: As variáveis idade e parada cardiorrespiratória (PCR) se mostraram como fatores de risco estatisticamente significativos para óbito - OR 1,04 (IC 95% 1,02 - 1,07) e p<0,001; OR 3,00 (IC 95% 1,01 - 8,92) e p=0,046, respectivamente. Não foi possível avaliar se DPG isoladamente se associaram a um desfecho desfavorável ou seriam um viés para o desenvolvimento de PCR nesses pacientes. Porém, dos seis casos de DPG isoladas, 2/3 evoluíram para óbito, o que revela uma tendência a pior prognóstico. Foi observada diferença significativa (p=0,031) para pior desfecho ao comparar o grupo de 28 pacientes que apresentou DPG ou PCR com o outro grupo que não apresentou nenhuma dessas variáveis, sendo que desses 28 pacientes, 20 (71,4%) foram a óbito. Conclusões: A presença de DPG pós-PCR está associada a pior prognóstico, porém não ficou claro se esses padrões são fatores independentes de evolução desfavorável.

Dyke-Davidoff-Masson syndrome and chiari type ii malformation / Síndrome de Dyke-Davidoff-Masson e malformação de chiari tipo II

Dyke-Davidoff-Masson Syndrome is a syndrome associated with refractory epilepsy. The Chiari II malformation is a complex congenital malformation of the brain. The authors report a case of a 15 years-old adolescent presenting Dyke-Davidoff-Masson syndrome and Chiari type II malformation association. This case demonstrates an unusual association in neuroimaging tests that indicates the need to evaluate associated diseases, such as myelomeningocele, corpus callosum dysgenesis and syringohydromyelia.

A Síndrome de Dyke-Davidoff-Masson é uma síndrome associada à epilepsia refratária. A malformação de Chiari II é uma malformação congênita complexa do cérebro. Os autores relatam um caso de uma adolescente de 15 anos apresentando a síndrome de Dyke-Davidoff-Masson associada à malformação de Chiari tipo II. Este caso demonstra uma associação incomum nos exames de neuroimagem que indica a necessidade de avaliar doenças associadas, como mielomeningocele, disgenesia do corpo caloso e a siringohidromielia.

Doenças do sistema nervoso central em cães / Central nervous system disorders diagnosed in dogs

São descritas doenças do sistema nervoso central (SNC) em cães diagnosticadas no sertão da Paraíba. Os registros de necropsia de 1.205 cães foram revisados. Em 354 casos (29,38%) foram registrados história clínica de alterações do sistema nervoso. Duzentos e noventa e seis casos tiveram diagnóstico definitivo e 58 foram inconclusivos. As doenças infecciosas foram observadas em 59,60% (211/354) de casos que representam a principal causa de distúrbios neurológicos; 53% dos casos (186/354) foram representadas por doenças virais; 3,11% (11/354) foram de etiologia parasitária, 2,54% (9/354) foram causadas por bactérias e 1,41% (5/354) por fungos. Os agentes físicos representaram a segunda causa mais importante de transtornos do SNC com 9,89% (35/354) e os tumores a terceira causa com 5,93% (21/354). Outras alterações pouco frequentes foram alterações metabólicas secundárias a insuficiência hepática ou renal, representando 2,54% (9/354). Casos raros de hidrocefalia congênita foram observados, 1,41% (5/354). Os casos de manifestações neurológicas associadas a alterações vasculares, degenerativas e inflamatórias não infecciosas, muitas das quais uma causa específica não foi estabelecida representaram 4,24% (15/354); Estavam dentro das seguintes categorias de doenças: Infartos isquêmicos e hemorrágicos (6/15), necrose vascular fibrinoide (5/15), doença do disco intervertebral (2/15), meningoencefalite granulomatosa (1/15) e granuloma de colesterol (1/15). Os distúrbios do sistema nervoso central representam uma importante causa de morte ou eutanásia em cães na região semiárida da Paraíba. Os sinais clínicos variaram de acordo com o agente envolvido, localização e distribuição das lesões. O conhecimento dos principais agentes que pode afetar o SNC canino é importante ao fazer uma lista de diagnóstico diferencial.(AU)

Central nervous system (CNS) diseases in dogs diagnosed in the backlands of Paraiba are described. The necropsy records of 1,205 of dogs were reviewed. In 354 cases (29.38%) a history of clinical alterations of the nervous system were recorded. Two hundred and ninety six cases had a definitive diagnosis and 58 were inconclusive. Infectious diseases were observed in 59.60% (211/354) of cases representing the main cause of neurological disorders; 53% of the cases (186/354) were represented by viral diseases; 3.11% (11/354) were of parasitic etiology, 2.54% (9/354) were caused by bacteria and 1.41% (5/354) by fungi. Physical agents represented the second most important cause of CNS disorders with 9.89% (35/354) and tumors third cause with 5.93% (21/354). Other uncommon observed disorders were metabolic changes secondary to liver or kidney failure, accounting for 2.54% (9/354). Rare cases of congenital hydrocephalus were observed, 1.41% (5/354). The cases of neurological manifestations associated with vascular, degenerative and inflammatory noninfectious lesions, for many of which were specific cause was not established accounted for 4.24% (15/354); they were within the following disease categories: ischemic and hemorrhagic infarcts (6/15), vasculitis fibrinoide necrosis (5/15), intervertebral disc disease (2/15), granulomatous meningoencephalitis (1/15) and cholesterol granuloma (1/15). The central nervous system disorders represent an important cause of death or reason for euthanasia in dogs in the semiarid region of Paraiba. Clinical signs vary according to the agent involved, and the location and distribution of the lesions. The knowledge of the main agents that can affect the canine CNS it is important when making a list of differential diagnosis.(AU)

Encefalopatía por virus herpes 6 como complicación de exantema súbito / Encephalopathy due to human herpesvirus 6 infection as exanthema subitum complication

La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.

The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.

Neurological Complications Resulting from Non-Oral Occupational Methanol Poisoning

Methanol poisoning results in neurological complications including visual disturbances, bilateral putaminal hemorrhagic necrosis, parkinsonism, cerebral edema, coma, or seizures. Almost all reported cases of methanol poisoning are caused by oral ingestion of methanol. However, recently there was an outbreak of methanol poisoning via non-oral exposure that resulted in severe neurological complications to a few workers at industrial sites in Korea. We present 3 patients who had severe neurological complications resulting from non-oral occupational methanol poisoning. Even though initial metabolic acidosis and mental changes were improved with hemodialysis, all of the 3 patients presented optic atrophy and ataxia or parkinsonism as neurological complications resulting from methanol poisoning. In order to manage it adequately, as well as to prevent it, physicians should recognize that methanol poisoning by non-oral exposure can cause neurologic complications.

Utility of Susceptibility-Weighted Imaging in Comatose Patients after Cardiac Arrest: A Preliminary Study

PURPOSE: This study was conducted to examine the efficacies of susceptibility weighted images (SWI) for predicting the clinical prognosis of comatose patients following cardiac arrest. METHODS: Thirty-two patients who were resuscitated from cardiac arrest and underwent brain magnetic resonance imaging (MRI) were retrospectively investigated and compared to 32 subjects with normal brain MRI findings who served as controls. The SWI readings were divided into three categories: prominent, diminished, and normal. Comatose patients were divided into two groups: those with a Glasgow-Pittsburgh cerebral performance category (CPC) of 1-2 (good outcome group) and those with a CPC of 3-5 (poor outcome group). RESULTS: Of the 32 patients, 17 (53.1%) showed good neurological outcomes upon hospital discharge. Normal patterns on SWI were mainly seen in the good outcome group (15 patients, 88.2%), while diminished patterns and prominent patterns were frequently found in the poor outcome group (13 patients, 88.7%). The combination of diminished pattern and prominent pattern predicted poor outcome with 86.7% sensitivity (95% confidence interval, 69.5%-100%) and 88.2% specificity (95% confidence interval, 72.9%-100%). CONCLUSION: The SWI findings correlate with the outcome of hypoxic-ischemic encephalopathy and may be a useful adjunct of vegetative state or death in comatose patients after cardiac arrest.

Lack of meaningful genotype-phenotype association in SCN1A-related infantile-onset epileptic encephalopathies

Background & Objective: SCN1A gene which encodes for sodium channel alpha 1 subunit has been found to be the most common mutated gene in patients with epilepsy. This study aims to characterize the SCN1A mutations as well as to describe genotype and phenotype association in children with SCN1Arelated infantile-onset epileptic encephalopathies in Malaysia. Methods: Children with infantile-onset epileptic encephalopathy mostly suspected to have Dravet syndrome who had mutational analysis for SCN1A gene from hospitals all over Malaysia were included in the study. Their epilepsy syndrome diagnosis was classified into severe myoclonic epilepsy in infancy and its variants. Polymerase chain reaction and bidirectional sequencing were used to identify SCN1A mutations. Results: A total of 38 children with heterozygous mutations were analysed, 22 (57.9%) of which were novel mutations. Truncated mutations were the most common mutation type (19, 50%). Other mutation types were missense mutations (14, 36.8%), splice site mutations (4, 10.5%) and in-frame deletion (1, 2.6%). The mean age of seizure onset was 4.7 months. Seizure following vaccination was observed in 26.3% of the children. All of them had drug resistant epilepsy. There was no significant association between the type of mutation with the syndromic diagnosis, age of seizure onset, tendency of the seizures to cluster or having status epilepticus, mean age when developmental delay was observed and response to various antiepileptic drugs. Conclusion: This study expands the spectrum of SCN1A mutations and proves the importance of SCN1A gene testing in diagnosing infantile-onset epileptic encephalopathies patients. Although, our study does not support any clinically meaningful genotype-phenotype association for SCN1A-related infantile-onset epileptic encephalopathies, the clinical characteristics of our cohort are similar to those that have been described in previous studies.

Teoría Prión - Enfermedades Priónicas / Prion Theory Prion Diseases

Un enorme progreso se ha logrado en la identificación, prevención, control y estudio de las enfermedades priónicas. El objetivo de esta actualización es presentar un breve Resumen de la historia de la Teoría Prión, de la participación nacional en relación con la salud humana y animal, así como algunos avances sobre la estructura molecular del amiloide priónico. Se explica, en parte, por qué hasta hoy solo tenemos en nuestro país presencia de la Enfermedad de Creutzfeldt-Jakob (ECJ) en su variedad esporádica y una ausencia comprobada de la Encefalopatía Espongiforme Bovina (EEB o "Enfermedad de las vacas locas"), lo que descarta la posible aparición de la variante de la ECJ (vCJ), de carácter zoonótico. Finalmente, como un avance reciente en investigación básica, se actualiza la evidencia experimental sobre una posible relación entre el amiloide de las enfermedades priónicas, el beta amiloide, ßA, de la enfermedad de Alzheimer y la alfa sinucleina de la enfermedad de Parkinson, que hasta hace muy poco se ha empezado a investigar. Se discute el mecanismo de neurotoxicidad, nucleación, transmisión del mal plegamiento y la restricción de su transmisión entre especies.

There has been tremendous progress in the identification, prevention, control and study of prion diseases. This update presents a brief Summary of the history of Prion theory and the national participation in relation to human and animal health, which may partly explain why we have presence in our country of Creutzfeldt-Jakob disease (CJD) only in its sporadic variant and an absence of bovine spongiform encephalopathy (BSE or "mad cow disease") until today. These also rule out the possible occurrence of variant CJD (vCJ), which is a zoonotic disease. Finally, as recent advances in basic research, we show a similarity in prion amyloid aggregate structure formed by prions, ßA amyloid aggregates of Alzheimer's disease and alpha synuclein of Parkinson disease, which until recently began being investigated. A mechanism of neural toxicity, nucleation, transmission misfolding and restriction of transmission between species is discussed.

Newer Anti-epileptic Drugs.

Need and Purpose of review: A number of newer anti-epileptic drugs have been developed in the last few years to improve the treatment outcomes in epilepsy. In this review, we discuss the use of newer anti-epileptic drugs in children. Methods used for locating, selecting, extracting and synthesizing data: MEDLINE search (1966-2013) was performed using terms “newer anti-epileptic drugs”, “Oxcarbazepine”, vigabatrin”, topiramate”, “zonisamide”, “levetiracetam”, “lacosamide”, “rufinamide”, “stiripentol”, “retigabine”, “eslicarbazepine”, “brivaracetam”, “ganaxolone” and “perampanel” for reports on use in children. Review articles, practice parameters, guidelines, systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and case series were included. The main data extracted included indications, efficacy and adverse effects in children. Main conclusions: Oxcarbazepine is established as effective initial monotherapy for children with partial-onset seizures. Vigabatrin is the drug of choice for infantile spasms associated with tuberous sclerosis. Lamotrigine , levetiracetam and lacosamide are good add-on drugs for patients with partial seizures. Lamotrigine may be considered as monotherapy in adolescent females with idiopathic generalized epilepsy. Levetiracetam is a good option as monotherapy for females with juvenile myoclonic epilepsy. Topiramate is a good add-on drug in patients with epileptic encephalopathies such as Lennox-Gastaut syndrome and myoclonic astatic epilepsy.

Polimorfismo do gene da proteína prion celular (PrPC) e imunohistoquímica de tecido linfóide em ovinos / Polymorphism of cellular prion protein (PrPC) and immunohistochemistry of lymphoid tissue of sheep

O objetivo deste trabalho foi avaliar o polimorfismo do gene da proteína prion celular (PRPN) de ovinos introduzidos numa propriedade onde ocorreu um surto de scrapie, e relacionar com a suscetibilidade à doença por meio da análise da presença da proteína prion celular alterada (PrPSc), utilizando imunohistoquímica (IHQ) de tecido linfóide associado à mucosa reto-anal. Foram avaliados 42 ovinos, mestiços Texel. Eram fêmeas entre um e oito anos de idade, sendo que sete (16,67%) ovelhas foram introduzidas adultas na propriedade em 2006. As demais, 83,33%, eram nascidas na fazenda. A genotipagem do PRPN foi feita pela análise do polimorfismo de comprimento de fragmento de restrição - RFLP ("Restriction Fragment Lenght Polimorphism"). O genótipo ARQ/ARQ foi o mais freqüente, encontrado em 73,81% dos animais, seguido do genótipo ARR/ARQ, com 16,67% e do ARQ/VRQ, com 9,52%. Os alelos ARH e AHQ não foram encontrados nestes animais. O resultado da IHQ foi negativo em todas as amostras. Não foi possível, portanto, estabelecer uma relação entre genótipo e maior susceptibilidade ao scrapie, devido à ausência de PrPSc na amostras examinadas. No Brasil, há poucos dados de genotipagem do gene da proteína prion celular (PRNP) em ovinos e, até o momento, nenhum tipo de controle baseado em cruzamentos direcionados foi implementado.

The aim of this work was to study the polymorphism of the prion protein gene (PRNP) of a sheep flock raised in a farm where a scrapie outbreak had occurred, and to relate to disease susceptibility of possible animals infected with altered prion protein (PrPSc), by immunohistochemical analysis of recto-anal mucosa-associated lymphoid tissue (RAMALT). Forty two sheep, crossbred with Texel, Ile de France, Dorper and Suffolk were used. Females were between one and eight years old, and seven (16.67%) were adult ewes when they entered the flock in 2006. The rest, 83.33% were born in the farm. The PRNP genotyping was performed by RFLP ("restriction fragment length polymorphism") analysis. The most frequent genotype was ARQ/ARQ, found in 73.81% of the animals, followed by ARR/ARQ, with 16.67% and ARQ/VRQ, with 9.52%. The ARH and AHQ alleles were not found. All RAMALT samples were negative in immunohistochemical analysis. It was not possible to establish a relation between PRNP polymorphisms and susceptibility to scrapie, due to the lack of positive samples to PrPSc. In Brazil, there is little available PRNP genotyping data of sheep and, so far, no type of controlled breeding scheme for scrapie has been implemented.

Genetic contribution to early-onset epileptic encephalopathies / 临床儿科杂志

10.3969/j.issn.1000-3606.2013.06.022

Genetic variability of the prion protein gene (PRNP) in wild ruminants from Italy and Scotland

The genetics of the prion protein gene (PRNP) play a crucial role in determining the relative susceptibility to transmissible spongiform encephalopathies (TSEs) in several mammalian species. To determine the PRNP gene variability in European red deer (Cervus elaphus), roe deer (Capreolus capreolus) and chamois (Rupicapra rupicapra), the PRNP open reading frame from 715 samples was analysed to reveal a total of ten single nucleotide polymorphisms (SNPs). In red deer, SNPs were found in codons 15, 21, 59, 78, 79, 98, 136, 168 and 226. These polymorphisms give rise to 12 haplotypes, and one of which is identical to the PRNP of American wapiti (Rocky Mountain elk, Cervus elaphus nelsoni). One silent mutation at codon 119 was detected in chamois and no SNPs were found in roe deer. This analysis confirmed that European wild ruminants have a PRNP genetic background that is compatible with TSE susceptibility, including chronic wasting disease.

Occupational hazard with “PRIONS”- in Autopsy workers.

Autopsy room as a potential source of infection to Forensic Pathologists / Autopsy Surgeons and other personnel assisting to conduct an autopsy is a well documented fact. Most frequently reported infections are tuberculosis, brucellosis, salmonellosis, HIV, hepatitis viruses (HBV, HCV etc). New worrisome infective agents called ‘PRIONS’ are associated with degenerative diseases of the central nervous system (CNS) in man and animals (e.g. Mad Cow Disease). Prions are proteinaecious infective agents characterized by extreme resistance to conventional inactivation procedures and transmissible through food, contaminated instruments etc.