[Paraneoplastic neurological syndromes]. / Les syndromes neurologiques paranéoplasiques.

Neurological paraneoplastic syndromes are non-metastatic complications of systemic cancers, often resulting from an immune response triggered by the crossed expression of neuronal antigens by tumour cells. Several neurological syndromes such as cerebellar degeneration, sensory neuronopathy, limbic encephalitis, encephalomyelitis or the Lambert-Eaton myasthenic syndrome are most often paraneoplastic and require prompt cancer screening, particularly if the patient shows risk factors for cancer. Although there are many exceptions to this rule, a given syndrome is often associated with a particular antibody and the corresponding tumour. A prompt diagnosis of neurological paraneoplastic syndrome is of major importance as it often reveals the underlying tumour. The treatment relies on both the elimination of the neoplasia and the control of the immune response.

Les syndromes neurologiques paranéoplasiques sont des complications neurologiques non métastatiques de cancers systémiques résultant, le plus souvent, d'une réaction immunitaire croisée dirigée contre des antigènes neuronaux membranaires ou intracellulaires. Certains de ces syndromes paranéoplasiques sont classiques comme les ataxies cérébelleuses, les neuronopathies sensitives ou ganglionopathies, l'encéphalite limbique, les encéphalomyélites ou le syndrome de Lambert-Eaton. Devant de tels tableaux cliniques, une étiologie paranéoplasique doit, surtout chez les patients présentant des facteurs de risque, être systématiquement recherchée. Bien que cette règle souffre de nombreuses exceptions, il y a souvent concordance entre un syndrome clinique spécifique, un type d'anticorps et une tumeur associée. Le diagnostic d'un syndrome neurologique paranéoplasique est essentiel puisqu'il révèle souvent le cancer sous-jacent. Le traitement comporte deux axes principaux : celui du cancer responsable et le contrôle de la réponse immunitaire.

Continuous infusion of cefepime and neurotoxicity: a retrospective cohort study.

OBJECTIVES: Neurotoxicity related to cefepime is increasingly reported in the literature but specific data concerning continuous infusion (CI) of the drug are still lacking. Our primary objective was to evaluate the incidence of neurotoxicity related to CI of cefepime and the associated risk factors. Our secondary objectives were to analyse the plasma cefepime concentrations and to define the threshold above which neurotoxicity occurs. METHODS: In this single-centre retrospective cohort study, all adult patients who underwent at least one cefepime therapeutic drug monitoring (TDM) and were treated with CI of 4 g/day between January 2017 and June 2019 were included. Neurotoxicity was evaluated according to a strict definition and was correlated with steady-state concentration at the time of toxicity presentation. RESULTS: Ninety-eight patients with 201 cefepime TDM studies were included, with an incidence of neurotoxicity of 14.3% (14/98). Patients with neurotoxicity had more often underlying brain disease (35.7% (5/14) vs 11.9% (10/84), p = 0.030)) and higher steady-state concentrations (mean ± standard deviation 71.8 ± 32.9 mg/L vs 49.6 ± 30.6, p = 0.036) than the others. A receiver operating characteristic curve analysis yielded a cefepime steady-state concentration of 63.2 mg/L as the best cut-off point between patients with or without neurotoxicity. A mean steady-state concentration of 46.4 mg/L was achieved if the dosages of cefepime were adapted to renal function which was under our threshold concentration but above our highest pharmacokinetic/pharmacodynamic target of 32-40 mg/L. CONCLUSIONS: Our results suggest that 4 g/day of cefepime adapted to renal function and infused over 24 h is a trade-off for the risk/benefit ratio, when used empirically.

Expression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis.

AIMS: Synaptic vesicle proteins 2 (SV2) are neuronal vesicles membrane glycoproteins that appear as important targets in the treatment of partial and generalized epilepsies. Therefore, we analysed the expression of SV2 isoforms in the hippocampus of patients with temporal lobe epilepsy (TLE). METHODS: SV2A, SV2B and SV2C immunostaining and QuantiGene branched DNA assay were performed on biopsies from 31 consecutive TLE patients with mesial temporal sclerosis (MTS) and compared with 10 autopsy controls. SV2 expression was further compared with Timm's staining, and synaptophysin, Zinc transporter 3 (ZnT3), dynorphin, vesicular glutamate transporter 1 (VGLUT1) and vesicular GABA transporter (VGAT) expression. RESULTS: In TLE patients, SV2A and SV2B expression was decreased in areas of synaptic loss. SV2C, which is weakly expressed or absent in the hippocampus of controls, was overexpressed in 10/11 cases with classical MTS1A and mossy fibre sprouting but not in cases with other types of MTS. SV2C staining was located in the inner molecular layer of the dentate gyrus and colocalized with dynorphin, ZnT3 and VGLUT1, suggesting selective expression in presynaptic glutamatergic Zn(2+) -rich terminals of abnormal sprouting fibres. SV2 expression patterns correlated with histological subtypes of MTS, but not with clinical features or therapeutic regimens in this patient cohort. CONCLUSION: In classical MTS1A, the expression of SV2 isoforms is altered with a marked decrease of SV2A and SV2B paralleling synaptic loss and a selective increase of SV2C in sprouting mossy fibres. These findings suggest a different physiology of sprouting synapses and the possibility to target them with SV2C-specific strategies.

Electrophysiological investigations of brain function in coma, vegetative and minimally conscious patients.

Electroencephalographic activity in the context of disorders of consciousness is a swiss knife like tool that can evaluate different aspects of cognitive residual function, detect consciousness and provide a mean to communicate with the outside world without using muscular channels. Standard recordings in the neurological department offer a first global view of the electrogenesis of a patient and can spot abnormal epileptiform activity and therefore guide treatment. Although visual patterns have a prognosis value, they are not sufficient to provide a diagnosis between vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS) patients. Quantitative electroencephalography (qEEG) processes the data and retrieves features, not visible on the raw traces, which can then be classified. Current results using qEEG show that MCS can be differentiated from VS/UWS patients at the group level. Event Related Potentials (ERP) are triggered by varying stimuli and reflect the time course of information processing related to the stimuli from low-level peripheral receptive structures to high-order associative cortices. It is hence possible to assess auditory, visual, or emotive pathways. Different stimuli elicit positive or negative components with different time signatures. The presence of these components when observed in passive paradigms is usually a sign of good prognosis but it cannot differentiate VS/UWS and MCS patients. Recently, researchers have developed active paradigms showing that the amplitude of the component is modulated when the subject's attention is focused on a task during stimulus presentation. Hence significant differences between ERPs of a patient in a passive compared to an active paradigm can be a proof of consciousness. An EEG-based brain-computer interface (BCI) can then be tested to provide the patient with a communication tool. BCIs have considerably improved the past two decades. However they are not easily adaptable to comatose patients as they can have visual or auditory impairments or different lesions affecting their EEG signal. Future progress will require large databases of resting state-EEG and ERPs experiment of patients of different etiologies. This will allow the identification of specific patterns related to the diagnostic of consciousness. Standardized procedures in the use of BCIs will also be needed to find the most suited technique for each individual patient.

[Facial nerve palsy. Not always that easy!]. / La vignette diagnostique de l'etudiant. La paralysie faciale ... pas toujours si facile que cela!

We report the case of a 45 years old woman who experienced two episodes of facial palsy, first on the left side, then on the other. This particular case allows us to discuss the diagnostic process and clinical reasoning to follow in front of this symptomatology -using a didactic questioning- and to briefly review the anatomy of the seventh cranial nerve. Treatment and possible complications are also discussed.

[Treatment compliance in epileptic patients. A frequent and complex problem]. / Le défaut d'observance thérapeutique du patient souffrant d'epilepsie. Un problème fréquent et complexe.

Epilepsy is a chronic disease, requiring a medical treatment which is essentially preventive (avoiding further seizure). Because of these characteristics, 30 to 50% of epileptic patients do not always comply with their treatment. In this paper, we review the different factors of poor compliance. Some are specific to this medical condition, while others are more general, like treatment complexity. We list some suggestions to improve the compliance of the epileptic patient in routine medical practice.

Primary diffuse leptomeningeal gliomatosis: an autopsy case and review of the literature.

We report a case of primary diffuse leptomeningeal gliomatosis (PDLG) in a 76-year-old male presenting with confusion, dysarthria, diplopia, lumbal pain and headaches of recent onset. Neurological examination revealed nuchal rigidity and bilateral sixth cranial nerve palsy. The cerebrospinal fluid showed a marked hyperproteinorachia (4711 mg/L) and mild cytorachia (5-10 leucocytes/mm3) with a few atypical lymphoid cells. On admission, brain CT scan and MRI demonstrated diffuse and nodular leptomeningeal contrast enhancement predominant at the skull base and several osteolytic lesions in the right parietal bone. Extensive serological studies for infectious, autoimmune or neoplastic diseases were negative. The work-up diagnosis was neurosarcoidosis or multiple meningeal and osseous metastases of an unknown primary cancer. Surgical biopsy of the right parietal bone lesion showed only fibrous tissue with no evidence of tumour or inflammation. The patient was treated with high dose corticosteroids but its neurological status progressively worsened and he died of aspiration pneumonia 35 days after admission. Post-mortem examination revealed a PDLG, a rare fatal tumour with about 60 cases reported. PDGL is characterized by the diffusion of neoplastic glial cells throughout the leptomeninges without evidence of a primary intra-parenchymal lesion. Recognition of this rare brain tumour is important as recent reports suggest that radiotherapy and chemotherapy can improve patient survival.

Opinion of Belgian neurologists on antiepileptic drug treatment in 2006: Belgian study on epilepsy treatment (BESET-2).

OBJECTIVES: (i) To describe the medical treatment of epilepsy in Belgium in 2006, (ii) to detect the presence or absence of consensus in epilepsy treatment and (iii) to analyze the evolution of the neurologists' opinion between 2003 and 2006. MATERIALS AND METHODS: In December 2006, 100 neurologists were interviewed with a structured questionnaire, based on ordinal four-point scales. The questionnaire contained questions on treatment choices in adult patients with epilepsy. The results of this survey were compared with results of a previous one done in 2003. RESULTS: Initial monotherapy was the preferred treatment strategy. Valproate was first choice in idiopathic generalized epilepsy. Carbamazepine and oxcarbazepine were first choice in focal epilepsy with partial seizures. Valproate was also first choice in focal epilepsy with secondarily generalized seizures. New antiepileptic drugs were recommended in second line. However, in special treatment situations, they were considered first-line, e.g. lamotrigine in case of women in childbearing age. In comparison with 2003, there was a trend of using earlier the new antiepileptic drugs. CONCLUSIONS: In end 2006, carbamazepine, valproate and oxcarbazepine were considered to be first choice drugs, whereas other newer drugs, like lamotrigine, levetiracetam and topiramate were predominantly prescribed in second line.

[When a seizure occurs...]. / Quand survient la crise d'epilepsie ...

With an apparently first epileptic seizure in a young female patient, we propose a diagnostic and therapeutic discussion on a common clinical problem. Due to the large number of available antiepileptic drugs, choosing the best treatment is not an easy task. One must take into consideration the type of epilepsy, the pharmacological properties of the antiepileptic drug, and the clinical profile of the patient. Besides drug prescription, specific recommendations must also be made.

[Confusion and unexplained fever in an elderly man: a case report]. / Le cas clinique du mois. Etat confusionnel et fièvre inexpliquée chez un vieillard.

We report the story of a 81 year old man referred for confusion and unexplained hyperthermia. He had no meningeal sign. Routine emergency examinations (CT scanner and lumbar punction) were not contributory, but, later, PCR for herpes virus was highly positive and cerebral CT scan showed the temporal lobe necrosis typical of an herpes virus meningoencephalitis. This severe neurologic emergency is then shortly discussed.

[Time is brain]. / Prise en charge de l'accident vasculaire cérébral ischémique à la phase aiguë.

Ischemic stroke exacts a heavy toll in death and disability. Important progress have been made in terms of secondary prevention. Care of patients with acute stroke can also be improved. In 1996, the FDA approved Alteplase or rt-PA as a safe and effective treatment for stroke when given within 3 hours of the onset of neurological deficit. More than 10 years later, this treatment is still underused, mostly because of poor knowledge in the general population regarding stroke symptoms and implications, and inefficient emergency care and organisation. Organisation of primary stroke centers results in optimization in the care of patients with acute stroke, and improvement in outcomes, with reduction in death, dependency and need for institutional care.

[Predicting prognosis in post-anoxic coma]. / Comment prédire l'évolution du coma post-anoxique?

Most patients who remain comatose for a few hours after a period of global cerebral ischemia have a poor prognosis. Early identification of these patients is desirable to reduce uncertainty about treatment and non-treatment decisions, and to improve relationships with the family. The absence of pupillary light response and corneal reflexes, absent or stereotyped extension motor response to noxious stimulation (3 days after insult); myoclonus status epilepticus; absence of cortical N20 response on somatosensory evoked potential studies; generalised suppression or burst-suppression EEG and serum neuron-specific enolase above 33 microg/L (sampled 1-3 days after insult) have been shown to predict poor outcome. We here propose an algorithm to help intensive care physicians' clinical decision making in post-anoxic coma.

[Statin for the brain: update in 2008]. / Des statines pour le cerveau. Le point en 2008.

Statins are essential drugs for the prevention of coronary artery disease. There is now evidence that they can also prevent ischemic stroke. The protective effect is related to the reduction in total and LDL cholesterol levels and the clinical benefit is especially high in secondary prevention patients with previous stroke and/or transient ischemic accident. The favourable role of statins is less well documented during an acute stroke than during an acute coronary syndrome, and certainly deserves further studies. Besides their specific cholesterol-lowering effect, statins exert various pleiotropic effects, which probably contribute to vascular protection. Furthermore, statins are able to reduce the formation of beta-amyloid peptide, which plays a key-role in the pathogenesis of Alzheimer disease. However, currently available results are heterogeneous and could not firmly support a protective effect of statins in dementia in general, neither in Alzheimer disease more specifically, nor in the reduction of cognitive function in the elderly. Several ongoing trials should confirm or not confirm this new potential indication of statins in a near future.

[Neuroborreliosis]. / La neuroborréliose: quand la tique a piqué.

Borrelia burgdorferi infection is a frequent disease in our country. The neurological complications of this infection are found essentially in the early dissemination stage and in the late stage of the disease. Neuroborreliosis symptoms are most often characterized by radiculalgia resisting to treatment, sometimes associated to a cranial neuropathy, predominantly facial. The evolution is satisfactory under adapted antibiotherapy. This antiobiotherapy remains necessary despite the fact that most neuroborreliosis complications resolve spontaneously. Treatment permits to avoid the appearance of late complications or of possible extraneurological symptoms.

[Therapeutic armamentarium in neurology: the birth of a new era]. / L'arsenal thérapeutique en neurologie: une nouvelle ère voit le jour.

The field of neurology was long infamous for a lack of therapeutic options. How many of you have once thought: "Neurologists don't cure the disease, they admire it". But those days have passed into history, and the field is now vibrant with new treatments and hope even for patients with the worst neurodegenerative diseases. We summarized in the present review the latest major advances in therapeutic principles and practice for some of the most frequent chronic neurological disorders such as headaches, epilepsy, multiple sclerosis, dementias, Parkinson's disease, sleep/wake disturbances and peripheral neuropathies. We cannot cure or prevent, but we can now halt or control symptoms and disease progression to provide physical and psychological relief, and a better quality of life for patients who suffer from these otherwise devastating neurological conditions.

[Cerebral autosomal dominant arteriolopathy with subcortical infarcts and leucoencephalopathy]. / Le CADASIL: une artériolopathie cérébrale sévère non exceptionnelle.

Cerebral Autosomal Dominant Arteriolopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is a recently but increasingly recognized cause of migraine with aura, early and recurrent strokes, and dementia, with an autosomal pattern of transmission. The disease is a widespread vasculopathy, but it is clinically expressed in the CNS only. Cerebral MRI is always abnormal in symptomatic patients, and sometimes in asymptomatic but affected individuals. It shows more or less confluent hypersignals on T2-weighted and flair images. A spectrum of mutations in the Notch3 gene on chromosome 19 are responsible for the disease. There is no specific treatment and the prognosis is poor. We followed three patients from 2 families with genetically confirmed CADASIL and we present their clinical characteristics. We discuss current data on this rare, but non exceptional arteriolopathy.

Opinion of Belgian neurologists on antiepileptic drugs: Belgian Study on Epilepsy Treatment (BESET).

OBJECTIVES: To describe the choice of treatment in adult patients with epilepsy in Belgium, to detect the presence or absence of consensus among neurologists in epilepsy treatment, and to analyze the gaps between current guidelines and prescriptions. MATERIALS AND METHODS: Hundred Belgian neurologists were systematically interviewed between May and June 2003 using a structured questionnaire (modified Rand method). RESULTS: Initial monotherapy was the preferred treatment strategy. Valproate was the first choice in idiopathic generalized epilepsy (IGE) and carbamazepine in focal epilepsy (FE). The new antiepileptic drugs (AED) were usually recommended in second-line. However, in special treatment situations, they were considered first-line, e.g., lamotrigine in case of women of childbearing age. CONCLUSIONS: Neurologists reached consensus for most questions on epilepsy treatment. In 2003, monotherapy with valproate and carbamazepine was the common treatment strategy in Belgium, whereas lamotrigine and to a lesser extent levetiracetam, topiramate, and oxcarbazepine were predominantly prescribed in second-line. This is in agreement with the recently published UK epilepsy guidelines but not in agreement, however, with the US guidelines, that for new onset epilepsy, new and old drugs are equally effective. Belgian neurologists, except for some special situations still prefer old drugs as first line.

Guidelines for the management of epilepsy in the elderly.

Seizures starting in patients over 60 years old are frequent. Diagnosis is sometimes difficult and frequently under- or overrated. Cerebrovascular disorders are the main cause of a first seizure. Because of more frequent comorbidities, physiologic changes, and a higher sensitivity to drugs, treatment has some specificity in elderly people. The aim of this paper is to present the result of a consensus meeting held in October 2004 by a Belgian French-speaking group of epileptologists and to propose guidelines for the management and the treatment of epilepsy in elderly people.

Efficacy and safety of levetiracetam in clinical practice: results of the SKATE trial from Belgium and The Netherlands.

OBJECTIVE: Aim of the study was to assess the efficacy and safety of levetiracetam as add-on treatment in patients with partial-onset epilepsy in clinical practice. METHODS: In this observational, multi-centre study patients were treated with levetiracetam for 16 weeks. From a starting dose of 1000 mg/day, dose levels were adjusted at 2-weekly intervals in 1000-mg steps, to a maximum of 3000 mg/day, based on seizure control and tolerance. Analysis of efficacy was based on reduction in seizure frequency relative to baseline, 50% and 100% responder rates (for partial seizures and all seizure types combined) and percentage of patients using levetiracetam at the end of the study. Analysis of safety was based on occurrence of adverse events. RESULTS: The present analysis concerns the results of patients recruited in Belgium and The Netherlands. Of the 251 patients included in the study, 86.9% completed 16 weeks of treatment. Reduction in frequency of partial-onset seizures was 62.2%, with 19.3% of the patients becoming seizure free and 56.6% having a reduction in seizure frequency of > or = 50%. These percentages were more or less the same when calculated for all seizure types combined. Tolerance of levetiracetam treatment was good, with most adverse events being only mild to moderate in severity, and only 10.0% of the adverse events leading to discontinuation from the study. Asthenia, somnolence, dizziness and headache were the most frequently reported adverse events. CONCLUSION: Levetiracetam is effective and safe as add-on treatment for partial-onset seizures in clinical practice.

Levetiracetam in a broad population of patients with refractory epilepsy: interim results of the international SKATE trial.

OBJECTIVE: To prospectively assess the safety and efficacy of levetiracetam in patients with uncontrolled focal epilepsy, in a common practice-based setting. PATIENTS AND METHODS: In this phase IV, open-label, 16-week community-based study, adult patients with focal seizures initially received levetiracetam 1,000 mg/day. Throughout the study, the dose was adjusted in increments of 1,000 mg (maximum 3,000 mg/day) to achieve seizure control and maintain tolerability. The outcome parameters were the percentage reduction in partial and total seizure frequency per week from historical baseline, global evaluation scale (GES), and adverse events (AE). RESULTS: Seven hundred and thirty-one patients were included in this analysis and 84.4% completed the study. The median percent reduction in all seizures was 47.8%, and 49.3% for all partial seizures. The 50% responder rate was 49%, and the seizure-free rate was 17.2% for all partial seizures. Approximately 60% of patients showed moderate to marked improvement on the GES. The majority of AE were of mild to moderate severity; the most commonly reported being asthenia, somnolence, headache, and dizziness. CONCLUSION: Levetiracetam is both efficacious and safe as an add-on therapy in patients with refractory epilepsy treated by clinicians in their daily practice.