Decreased benzodiazepine receptor and increased GABA level in cortical tubers in tuberous sclerosis complex

Purpose

To elucidate the functional characteristics of cortical tubers that might be responsible for epilepsy in tuberous sclerosis complex (TSC), proton magnetic resonance spectroscopy (¹H-MRS) and [123I] iomazenil (123I-IMZ) single photon emission computed tomography (SPECT) were performed.

Methods

¹H-MRS using a clinical 3-tesla magnetic resonance imager was performed in four children with TSC and 10 age-and sex-matched healthy control subjects. A single voxel was set on the right parietal lobe in control subjects. In patients with TSC, a single voxel was set on the epileptogenic tuber in the parietal or temporal lobe, and another voxel was set on the contralateral normal-appearing brain region. N-Acetylaspartate (NAA), myo-Inositol (mIns) and Glutamate (Glu) were analyzed using a conventional STEAM (Stimulated Echo Acquisition Mode) method. The concentration of gamma-aminobutyric acid (GABA) was quantified using MEGA-Point Resolved Spectroscopy (PRESS). Interictal 123I-IMZ SPECT was examined in all four patients with TSC.

Results

A significant decrease in the NAA concentration and significant increases in the mIns and GABA concentrations were detected in the cortical tubers of all 4 patients. No significant difference was observed in Glu concentrations. In all of the cortical tubers detected by magnetic resonance imaging, 123I-IMZ binding was significantly decreased.

Conclusion

Epileptogenesis in TSC might be caused by decreased inhibition secondary to the decrease in GABA receptors in dysplastic neurons of cortical tubers. An increase in the GABA concentration may compensate for decreased inhibition.     

Different MRI-defined tuber types in tuberous sclerosis complex: Quantitative evaluation and association with disease manifestations

Background

Tuberous sclerosis complex (TSC) is a rare genetic disorder with multisystem involvement. A magnetic-resonance (MRI) based classification of tubers into types A, B and C has been proposed. However, the relationship between different tuber types and their quantitative characteristics, also the non-neurological manifestations of TSC remains unknown.

Correlation of autism with temporal tubers in tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an inherited genetic disorder commonly associated with neuropsychiatric complications like epilepsy, mental retardation, autism and other behavioral problems and constitutes about 1-4% of the autistic population. Mental retardation and seizures, particularly infantile spasms are significant risk factors for the development of autism. Patients of TSC with autism are more likely to have temporal tubers than those cases without autism. We describe clinical and neuroimaging features of two such cases of tuberous sclerosis with autism.     

Correlación entre las lesiones desmielinizantes y el deterioro de las funciones ejecutivas en una muestra de pacientes mexicanos con esclerosis múltiple

Background

Multiple Sclerosis (MS) is characterised by several neurological symptoms including cognitive impairment, which has recently been the subject of considerable study. At present, evidence pointing to a correlation between lesion characteristics and specific cognitive impairment is not conclusive.

Objective

To investigate the presence of a correlation between the characteristics of demyelinating lesions and performance of basic executive functions in a sample of MS patients.

Patients and methods

We included 21 adult patients with scores of 0 to 5 on the Kurtzke scale and no exacerbations of the disease in at least 3 months prior to the evaluation date. They completed the Stroop test and the Wisconsin Card Sorting Test (WCST). The location of the lesions was determined using magnetic resonance imaging (MRI) performed by a blinded expert in neuroimaging.

Results

Demyelinating lesions were more frequently located in the frontal and occipital lobes. The Stroop test showed that as cognitive demand increased on each of the sections in the test, reaction time and number of errors increased. On the WCST, 33.33% of patients registered as having moderate cognitive impairment. No correlation could be found between demyelinating lesion characteristics (location, size, and number) and patients’ scores on the tests.

Conclusion

Explanations of the causes of cognitive impairment in MS should examine a variety of biological, psychological, and social factors instead of focusing solely on demyelinating lesions.     

Les auteurs de violences sexuelles en unité pour malades difficiles

Introduction

Literature concerned with the care of the mental patients perpetrators of sexual violence in psychiatric high security care unit is sparse and fragmented. According to studies, it is reported that a small proportion of such patients that suffer are between 3 and 5%. These patients are described as perverse and incurable and no subject to any treatment with the exception of surveillance in institutional settings. Based on the observation of an ancient literature and limited, our aim was to realize a study covering the year 2010. This proportion, has it changed? What are the profiles of sexual offenders in this care unit?

Material and method

We realized a retrospective study with all patients who were hospitalized in care unit for dangerous patients covering the year 2010 in Sarreguemines. We studied a sample of 124 patients who were all in forced hospitalization. We identified forensic history, judicial history, and sexual violence history for every patients who were studied.

Results

Sexual violence concerns only 10% of transfers in care unit for dangerous patients over the period studied. In this case, it's mainly sexual assaults occurring in community settings and not psychiatric. Sexual violence constitutes an indication of the forced hospitalization then transfer in this care unit. However, we find history of sexual violence in nearly 30% of patients being hospitalized in the care unit. It's primarily mental retardation closely followed by schizophrenia. These patients with history of sexual violence have important comorbidities: consumption of toxic and personality disorder. Finally, the prevalence of paraphilias remains low and only concerns 16% of sexual offenders in psychiatric high security care unit.

Discussion

It was admitted in literature that patients perpetrators of sexual violence were infrequent in dangerous patient care unit especially sexual perverts. Against all odds, one third of patients hospitalized in this care unit have committed sexual assault (a large proportion). More than half of these patients with mental retardation, schizoaffective disorder, bipolar disorder or personality disorder. Only 13% of schizophrenic patients have committed sexual violence: it's a small proportion compared to other mental illnesses.

Conclusion

The profile of sexual pervert exists in psychiatric high security care unit (sexual homicide with torture and barbaric act) but it's an uncommon cases. Sexual violence is frequent among hospitalized patient in psychiatric high security care unit (sexual violence found are varied: sexual touching, attempted rape of a nurse).     

La rééducation du membre supérieur assistée par robot contribue-t-elle à améliorer le pronostic de l’hémiparésie vasculaire ?

Introduction

Upper limb robot-assisted rehabilitation is a novel physical treatment for neurological motor impairments. During the last decade, this rehabilitation option utilizing technological tools has been evaluated in hemiparetic patients, mostly after stroke.

State of art

Studies at acute and chronic stages suggested good tolerance and a significant and persistent reduction of motor impairment; a real impact on disability has been shown in acute/sub acute patients.

Perspectives

Improved access to rehabilitation robots and an optimal use will probably be associated with higher efficiency of rehabilitative work in the paretic upper limb.

Conclusions

Even if this treatment is still confined to a narrow circle of users, the device's biomechanical properties and clinical suggestions from the literature may show promise for the future of rehabilitation.     

Épilepsie et santé de la reproduction : cohorte sénégalaise

Introduction

Epilepsy is a public health problem in Senegal and Africa because of its severity and its social importance. It occurs at any age sparing no sex. It can influence sexual life and reciprocally. Our aims were to study the effects of antiepileptic drugs on the sexual lives of women with epilepsy, the influence of these drugs on pregnancy and breastfeeding.

Methods

We conducted a prospective study from 1st March to 31st August 2011 in the neurological department of the Fann-Dakar teaching hospital Senegal. Only women with epilepsy were included.

Results

We collected 120 patients aged 16–64 years with a mean age of 30.58 years, 45% married, 44.16% were uneducated preponderant. All patients were taking antiepileptic drugs, 89.16% was alone. Fifty-five percent of our patients had epilepsy for at least 6 years; 45.83% had generalized epilepsy; 44.17% of partial seizures. In our cohort, 64.16% were under phenobarbital, 69.16% had good adherence. As side effects of drugs, 90% had sexual problems. Seventy-five percent enjoyed an active sex life. A decrease in the number of sex per week for the disease [31/55 = 56.66%] was noted. In addition, 51.17% were using contraception, including 38.7% of oral kind and 64.86% had noticed an increase in seizure frequency during their pregnancies. Of the 74 women who had contracted a pregnancy, 41.89% had premature infants, 16.21% have made abortions and 61.17% had psychosocial life affected.

Discussion and conclusion

People with epilepsy often experience sexual problems that may be caused by epilepsy, antiepileptic and/or reactions of the partner and the other facing the diagnosis of epilepsy.     

Traitement d’induction dans la sclérose en plaques : place du natalizumab

Background

Current treatment options for first-line immunotherapy in relapsing-remitting multiple sclerosis (MS) are recombinant interferon-β and glatiramer acetate. However, these therapies are only partially effective and certain patients may fail to respond. For this reason, it is important to elaborate alternative treatment strategies. Induction therapy represents a more aggressive approach in which powerful drugs are used right from the beginning to tackle the disease process hard and early. Natalizumab is a powerful monoclonal antibody approved for the treatment of relapsing-remitting MS and is known to silence disease activity.

Methods

We describe here the early outcome at 1 month and at 6 months of three patients treated with natalizumab for relapsing-remitting MS.

Results

All three patients had a high disease activity before the initiation of natalizumab, with 4, 8 and 5 gadolinium-enhancing lesions on brain MRI respectively. On the MRI scans made at 1 month after the first infusion, and at 6 months, there was no more gadolinium-enhancement and no new T2-lesion. Clinically, they did not experience any relapse.

Discussion

In these three cases, natalizumab showed a dramatic efficacy: the patients became “disease activity free” right from the first infusion. To our knowledge, natalizumab is not classically used as an induction therapy, unlike mitoxantrone. However, this treatment has potential hematological and cardiac toxicity and its use can be limited. Thus, in JC virus negative patients, natalizumab could be an interesting alternative treatment.

Conclusion

Our report suggests that induction strategy with natalizumab may be applicable in patients with aggressive multiple sclerosis. A study of more similar cases may be interesting to confirm these preliminary results.     

MECP2 duplication syndrome in both genders

Background

Duplications involving the methyl-CpG-binding protein 2 gene (MECP2) locus at Xq28 have been frequently identified in male patients who exhibit a phenotype unique from that of Rett syndrome, which is mainly characterized by severe mental retardation, recurrent infections, and epilepsy. This combination of features is recognized as MECP2 duplication syndrome.

Methods

Genomic copy number was investigated for patients with unexplained mental retardation, and phenotypic features of the patients having interstitial duplications including MECP2 were analyzed.

Results

Three male and one female patients with MECP2 duplication were identified. The phenotypic features of all the four patients were compatible with MECP2 duplication syndrome. The X-chromosome inactivation (XCI) pattern was analyzed in the female patient, identifying a skewed XCI that activated the X-chromosome containing the MECP2 duplication. Her mother possessed the same MECP2 duplication and a random XCI pattern but exhibited no phenotypic features, indicating a nonsymptomatic carrier. The brain magnetic resonance imaging revealed periventricular cystic lesions in all four patients, including the female patient.

Conclusion

This study suggested clinical implications of the MECP2 duplication syndrome not only in the male but also in female patients with unexplained mental retardation.     

Acute ischemic stroke treatment and the occurrence of seizures

Background and objectives

Early intravenous treatment with recombinant tissue plasminogen activator (rt-PA) improves the outcome of patients with an acute ischemic stroke. This retrospective observational study analyses whether rt-PA treatment also prevents the occurrence of early- and late-onset seizures.

Patients and methods

Thirty-eight patients treated with rt-PA were compared to 269 receiving anticoagulants (ACs) and 769 on antithrombotics (ATs) for an acute cardiac- or thrombo-embolic stroke. The epidemiological and clinical data, and the vascular risk factors were determined in the three groups. The incidence, onset and types of seizures were compared.

Results

The patients treated with rt-PA had more severe stroke signs on admission and remained more dependent than those treated with ACs and ATs. The appearance of early-onset seizures was related to the severity of the stroke. The incidence of the late-onset ones tended to be low in the rt-PA group. None of the patients developed status epilepticus or epilepsy.

Conclusion

The occurrence of early-onset seizures in the rt-PA treated group is related to the severity of the stroke and not to the treatment modality. Thrombolysis prevents partly the occurrence of late-onset seizures, probably, by a better reperfusion of the ischemic brain regions.     

Neuroimagen estructural y funcional en las enfermedades priónicas humanas

Introduction

Prion diseases are neurodegenerative disorders resulting from the accumulation of a misfolded isoform of the cellular prion protein (PrPc). They can occur as acquired, sporadic, or hereditary forms. Although prion diseases show a wide range of phenotypic variations, pathological features and clinical evolution, they are all characterised by a common unfavourable course and a fatal outcome.

Review summary

Some variants, such as kuru, have practically disappeared, while others, for example the variant Creutzfeldt-Jakob (vCJD) or those attributable to iatrogenic causes, are still in force and pose a challenge to current medicine. There are no definitive pre-mortem diagnostic tests, except for vCJD, where a tonsil biopsy detects 100% of the cases. For this reason, diagnostic criteria dependent on statistical probability have had to be created. These require complementary examinations, such as an electroencephalogram (EEG) or the detection of 14-3-3 protein in cerebrospinal fluid (CSF). Only the pulvinar sign in magnetic resonance imaging (MRI) has been included as a vCJD diagnostic criterion. The present review discusses neuroimaging findings for each type of prion disease in patients with a definitive histopathological diagnosis.

Conclusions

The aim is to define the usefulness of these complementary examinations as a tool for the diagnosis of this family of neurodegenerative diseases.     

Repeated seizures induce prefrontal growth disturbance in frontal lobe epilepsy

Background

The possible consequences of seizures in the immature brain have been the subject of much conjecture. We prospectively measured frontal and prefrontal lobe volumes using three-dimensional (3D) magnetic resonance imaging (MRI)-based volumetry in patients with frontal lobe epilepsy (FLE) presenting with the same seizure semiology. The pathogenesis of repeated seizure-induced brain damage is discussed herein.

Methods

Serial changes in regional cerebral volumes were measured in two patients with FLE presenting with intractable clinical courses and cognitive impairments/behavioral problems (FLE(+)) and four FLE patients without cognitive impairments/behavioral problems (FLE(−)). Eleven normal subjects (4–13 years old) served as controls. Volumes of the frontal and prefrontal lobes were determined using a workstation, and the prefrontal-to-frontal lobe volume ratio was calculated.

Results

Frontal and prefrontal lobe volumes revealed growth disturbance in FLE(+) compared with those of FLE(−) and control subjects. In addition, prefrontal-to-frontal lobe volume ratio increased serially in FLE(−) similarly to controls, but was stagnant or decreased in FLE(+). Prefrontal growth also revealed more rapid recovery in a FLE(+) patient with shorter active seizure period.

Conclusion

These findings suggest that repeated seizures may lead to prefrontal growth disturbance. The occurrence of frequent seizures in patients with FLE may be associated with prefrontal lobe growth retardation, which relates to neuropsychological problems and ultimate neuropsychological outcome.     

Manifestaciones neurológicas de los mixomas cardiacos. Experiencia en un centro de referencia

Introduction

Cardiac myxoma is an important but uncommon cause of stroke in younger patients. Few published case series analyse the frequency and clinical presentation of neurological complications in patients with myxoma.

Objective

To list all neurological complications from cardiac myxoma recorded in our hospital in the past 28 years.

Patients and methods

We retrospectively reviewed the neurological manifestations of cardiac myxoma in patients treated in our hospital between December 1983 and March 2012.

Results

Of the 36 patients with cardiac myxoma, 8 (22%) presented neurological manifestations. Half were women and mean age of patients was 52.4 ± 11.6 years. Sudden-onset hemiparesis was the most frequent neurological symptom (63%). Established ischaemic stroke was the most common clinical manifestation (75%), followed by transient ischemic attack. The most commonly affected territory corresponded to the middle cerebral artery. Myxoma was diagnosed by echocardiography in all cases. Mean myxoma size was 4.1 cm and most of the tumours (63%) had a polypoid surface. All tumours were successfully removed by surgery. There were no in-hospital deaths.

Conclusions

Cardiac myxomas frequently present with neurological symptoms, especially ischaemic events (established stroke or transient ischaemic attack), in younger patients with no cardiovascular risk factors. The anterior circulation is more frequently affected, especially the middle cerebral artery. Echocardiography can facilitate prompt diagnosis and early treatment of the lesion.     

Impact du niveau d’activité physique sur l’alexithymie et le coping dans une population de plus de 40 ans atteinte de sclérose en plaques : une étude pilote

Introduction

The aim of this study was to evaluate the impact of physical activity on alexithymia and coping strategies among people with multiple sclerosis aged over 40. The hypotheses were that physical activity should have a protective effect on alexithymia, and more particularly, on “emotional identification” and could influence coping strategies because it can be considered as a distractive coping strategy.

Methods

Thirty-seven patients aged 40 years or older were asked to complete a form including an identification sheet and standardized questionnaires: the Bermond-Vorst Alexithymia Questionnaire (version B), the Coping with Health Injuries and Problem Questionnaire, the Fatigue Impact Scale, and the Hospital Anxiety and Depression Scale.

Results

The participants with a high or moderate level of physical activity used “information research” as a coping strategy better than those who had a lower level of physical activity. They also analyzed their emotions better. The results revealed an association between these variables and anxiety, depression and fatigue.

Discussion

This study provides insight for future research about the impact of physical activity on multiple sclerosis.     

Psicosis epiléptica periictal,una causa de psicosis reversible

Introduction

Epileptic psychoses are categorised as peri-ictal and interictal according to their relationship with the occurrence of seizures. There is a close temporal relationship between peri-ictal psychosis and seizures, and psychosis may present before (preictal), during (ictal) or after seizures (postictal). Epileptic psychoses usually have acute initial and final phases, with a short symptom duration and complete remission with a risk of recurrence. There is no temporal relationship between interictal or chronic psychosis and epileptic seizures. Another type of epileptic psychosis is related to the response to epilepsy treatment: epileptic psychosis caused by the phenomenon of forced normalisation (alternative psychosis), which includes epileptic psychosis secondary to epilepsy surgery. Although combination treatment with antiepileptic and neuroleptic drugs is now widely used to manage this condition, there are no standard treatment guidelines for epileptic psychosis.

Clinical cases

We present 5 cases of peri-ictal epileptic psychosis in which we observed an excellent response to treatment with levetiracetam. Good control was achieved over both seizures and psychotic episodes. Levetiracetam was used in association with neuroleptic drugs with no adverse effects, and our patients did not require high doses of the latter.

Conclusions

Categorising psychotic states associated with epilepsy according to their temporal relationship with seizures is clinically and prognostically useful because it provides important information regarding disease treatment and progression. The treatment of peri-ictal or acute mental disorders is based on epileptic seizure control, while the treatment of interictal or chronic disorders has more in common with managing disorders which are purely psychiatric in origin. In addition to improving the patient's quality of life and reducing disability, achieving strict control over seizures may also prevent the development of interictal psychosis. For this reason, we believe that establishing a treatment protocol for such cases is necessary.     

Clinical and ictal characteristics of infantile seizures: EEG correlation via long-term video EEG monitoring

Purpose

The semiology of infantile seizures often shows different characteristics from that of adults. We performed this study to describe clinical and ictal characteristics of infantile seizures at less than two years of age.

Methods

A retrospective study was done for infants with epilepsy (ages: 1–24 months) who underwent long-term video electroencephalography (EEG) monitoring at Samsung medical center between November 1994 and February 2012. We analyzed the clinical and ictal characteristics of the 56 cases from 51 patients.

Results

In 69% of the patients, the seizure onset was before six months of age and the etiology was symptomatic in one third of the patients. Twelve seizure types were identified; spasms (24%), unilateral motor seizures (18%), and generalized tonic seizures (15%) were the three frequent types of seizure.All partial seizures were well correlated with the partial-onset ictal EEG, however 19.4% (7/36) of clinically generalized seizures revealed partial-onset ictal EEG. About one-thirds (4/11) of generalized tonic seizures had its ictal onset on unilateral or bilateral frontal areas and two out of seven generalized myoclonic seizures showed unilateral frontal rhythmic activities. Hypomotor seizures mainly arose from the temporal areas and hypermotor seizures from the frontal regions.

Conclusions

Even though most of the seizure semiology of infants is well correlated with ictal EEG, some of the generalized tonic seizures or myoclonic seizures revealed partial-onset ictal EEG suggesting localized epileptic focus. Accurate definition of seizures via video EEG monitoring is necessary for proper management of seizures in infancy, especially in some clinically generalized seizures.     

Hamartoma hipotalámico en la edad pediátrica: características clínicas,evolución y revisión de la literatura

Objective

To describe the epidemiological and clinical-electroencephalographic characteristics, and associated morbidity of patients with hypothalamic hamartoma, as well as the treatment followed and outcomes

Patients and methods

We have retrospectively reviewed the medical histories of 10 patients diagnosed with hypothalamic hamartoma by magnetic resonance imaging over the last 20 years.

Results

The age of onset of epilepsy in patients with hypothalamic hamartoma in our series was between the first days of life and 2 years. Of the 10 total patients, 8 had epileptic seizures during its progress. All of them had gelastic seizures, in addition to other types of seizures, with the most common being partial simple seizures. The electroencephalographic findings recorded were highly variable. One of the patients developed epileptic encephalopathy. Five patients had some kind of conduct disorder. Five patients had cognitive problems. At least 2 different antiepileptic drugs were measured in 8 of the patients who had seizures, and in 6 of these some type of non-pharmacological treatment had been used with the objective of seizure control. Only in 3 of 8 patients has been achieved Acceptable control of epilepsy had only been achieved in 3 out the 8 patients. Five patients of the series developed precocious puberty. The average time of follow-up of the series was approximately 6 years.

Conclusions

Epilepsy is the most frequent manifestation of hypothalamic hamartomas. Most cases were drug-resistant, which led to difficulties in the management of these patients, requiring surgery for their control on many occasions. Psychiatric comorbidity and cognitive impairment is common.     

Tratamiento del dolor orofacial en pacientes con síndrome del ligamento estilomandibular (síndrome de Ernest)

Introduction

Ernest syndrome involves the stylomandibular ligament. It is characterised by pain in the preauricular area and mandibular angle, radiating to the neck, shoulder, and eye on the same side, and associated with pain during palpation of that ligament. The purpose of this study is to describe the clinical characteristics, treatment, and course of the disease in a series of patients with Ernest syndrome.

Methods

Retrospective observational study covering the period from 1998 to 2008. We recorded patients’ age, sex, duration of the disorder, and pain characteristics. All patients were injected with 40 mg triamcinolone acetonide at the mandibular insertion of the stylomandibular ligament.

Results

The study included a total of 6 patients. Mean age was 40.3 years (range, 35-51). All of the subjects were women. Four patients had undergone lengthy dental treatments in the month prior to onset of the pain. The mean time between pain onset and first consultation was 23 months. The syndrome resolved completely in all cases after treatment, with a minimum follow-up period of 12 months.

Conclusions

We analysed the clinical characteristics, treatment, and course of disease in 6 patients with Ernest syndrome. Correct diagnosis is the key to being able to provide proper treatment. This disorder is sometimes confused with other types of orofacial pain, and may therefore be more prevalent than the literature would indicate.     

Dilatations géantes des espaces de Virchow-Robin symptomatiques

Introduction

Perivascular spaces, known as Virchow-Robin spaces (VRS), may become massively enlarged but are usually an incidental finding. However, a few reports on patients with unusually large VRS have mentioned association with neurological symptoms. We report a series of three symptomatic patients with extremely wide Virchow-Robin spaces documented on brain magnetic resonance imaging (MRI).

Methods

We retrospectively analyzed the medical records and brain MRI of three symptomatic patients, who had been diagnosed with VRS widening.

Case reports

In all three patients, the unusual widening of the VRS was located within the subcortical white matter with asymmetric distribution. Their neurological symptoms were epilepsy and neurological deficits which correlated well with the lesions seen on the MRI. Two patients had associated white matter hyperintensities: in the first case associated gliosis and in the second case, with vascular leukoencephalopathy.

Conclusions

Enlarged symptomatic VRS are rare. The underlying pathophysiological mechanisms remain uncertain. We report three cases with symptomatic giant dilatation of the Virchow-Robin spaces.