Simona Binelli

Infantile neuroaxonal dystrophy Clinical spectrum and diagnostic criteria

Objective: To present clinical, neurophysiologic, and neuroradiologic findings in 13 patients with infantile neuroaxonal dystrophy (INAD), focusing on aspects that assist early diagnosis. Background: Clinicopathologic diagnostic criteria for INAD were delineated by Aicardi and Castelein in 1979, but atypical cases are reported frequently and little is known of the diagnostic utility of MRI. Methods: The authors reviewed the clinical, neurophysiologic, and MRI findings of 13 patients who met the diagnostic criteria for INAD. Results: Symptoms onset was between 6 months and 2 years of age. In nine patients the clinical course was typical, with rapid motor and mental deterioration; in four patients progression was slower and the clinical picture was different. Electromyographic (EMG) signs of chronic denervation, fast rhythms on EEG and abnormal visual evoked potentials were observed in all patients during the disease course. Cerebellar atrophy with signal hyperintensity in the cerebellar cortex on T2-weighted images were the most characteristic MRI findings; hypointensity in the pallida and substantia nigra was also observed in two patients. α-N-acetyl-galactosaminidase activity on leukocytes was normal in the 10 patients tested. Conclusions: EMG and MRI abnormalities are the earliest and most suggestive signs of INAD, which has a clinical and radiologic spectrum that is broader than reported previously.

Dravet syndrome: Early clinical manifestations and cognitive outcome in 37 Italian patients

Aims of our study were to describe the early clinical features of Dravet syndrome (SMEI) and the neurological, cognitive and behavioral outcome. The clinical history of 37 patients with clinical diagnosis of SMEI, associated with a point mutation of SCN1A gene in 84% of cases, were reviewed with particular attention to the symptoms of onset. All the patients received at least one formal cognitive and behavior evaluation. Epilepsy started at a mean age of 5.7 months; the onset was marked by isolated seizure in 25 infants, and by status epilepticus in 12; the first seizure had been triggered by fever, mostly of low degree in 22 infants; the first EEG was normal in all cases. During the second year of life difficult-to-treat seizures recurred, mostly triggered by fever, hot bath, and intermittent lights and delay in psychomotor development became evident. At the last evaluation, performed at a mean age of 16+/-6.9 years, mental retardation was present in 33 patients, associated with behavior disorders in 21. Our data indicate that the most striking features of SMEI are: the early onset of seizures in a previously healthy child, the long duration of the first seizure, the presence of focal ictal symptoms, and sensitivity to low-grade fever. Diagnosis of SMEI may be proposed by the end of the first year of life, and a definite diagnosis can be established during the second year based on the peculiar seizure-favoring factors, EEG photosensitivity and psychomotor slowing. The temporal correlation between high seizure frequency and cognitive impairment support the role of epilepsy in the clinical outcome, even if a role of channelopathy cannot be ruled out.

Periodic electroencephalogram complexes in a patient with variant Creutzfeldt–Jakob disease

Based on the current criteria, the diagnosis of “possible” or “probable” variant Creutzfeldt–Jakob disease (vCJD) implies the absence of periodic sharp wave complexes (PSWCs) in the electroencephalogram (EEG). To verify this point, we investigated the development of the EEG changes along the course of the disease in a pateint with vCJD.

Focal epilepsies in adult patients attending two epilepsy centers: classification of drug-resistance, assessment of risk factors, and usefulness of "new" antiepileptic drugs

Purpose:  To classify the grade of antiepileptic drug (AED) resistance in a cohort of patients with focal epilepsies, to recognize the risk factors for AED resistance, and to estimate the helpfulness of “new‐generation” AEDs.

Myoclonus in Creutzfeldt-Jakob disease: polygraphic and video-electroencephalography assessment of 109 patients.

We used electroencephalography (EEG)‐polygraphic recordings to classify myoclonus in 109 patients with Creutzfeldt‐Jakob disease (CJD) on the basis of its electromyography (EMG) pattern, time course, distribution, and EEG correlates. We recorded myoclonic jerks in 55 patients (50.4%), and we classified them as periodic myoclonus in 28, rhythmic in 13, and irregular in 20 (6 patients showed two types of myoclonus). Myoclonus occurred as a prominently negative event (interrupting the EMG discharge) in 10. Periodic sharp‐wave complexes (PSWCs) were present in all but one patient with myoclonic jerks but were time‐locked with EMG‐bursts only in case of periodic myoclonus. Jerk‐locked back averaging revealed a variable EEG‐EMG transfer‐time commonly exceeding that characterizing cortical myoclonus. Myoclonus was frequently associated with Met/Met polymorphism at codon 129 of the prion protein gene, but it was also observed in association with Met/Val or Val/Val polymorphisms provided that the EEG showed the presence of the PSWC pattern. The presence of enlarged somatosensory evoked potentials significantly correlated with the myoclonic presentation, as did MR signal hyperintensity involving the cortical mantle. Our observations on the basis of standard polygraphic criteria suggest that CJD associates with a remarkable variety of myoclonic jerks, and therefore different brain structures are probably involved as generators. The significant association between the presence of all myoclonus types with PSWCs suggests that hyperexcitable corticosubcortical loops are always required to generate (or allow) both myoclonus and the EEG complexes, either they are time locked or not.

Ictal EEG fast activity in west syndrome : From onset to outcome

Purpose: To characterize the fast EEG activities associated with infantile spasms in West syndrome, and their value in predicting the recurrence and localization of late seizures.

A novel phenotype of sporadic Creutzfeldt-Jakob disease

An atypical case of sporadic Creutzfeldt–Jakob disease (CJD) is described in a 78-year-old woman homozygous for methionine at codon 129 of the prion protein (PrP) gene. The neuropathological signature was the presence of PrP immunoreactive plaque-like deposits in the cerebral cortex, striatum and thalamus. Western blot analysis showed a profile of the pathological form of PrP (PrPSc) previously unrecognised in sporadic CJD, marked by the absence of diglycosylated protease resistant species. These features define a novel neuropathological and molecular CJD phenotype.

Refractory Absence Epilepsy and Glut1 Deficiency Syndrome: A New Case Report and Literature Review

We report a 12-year-old female patient with a mild phenotype of glucose transporter type 1 deficiency syndrome (Glut1D). The clinical picture was characterized by refractory absence epilepsy, migraine, and learning disabilities. Absence seizures appeared at the age of 4 years, and electroencephalogram (EEG) showed irregular discharges of diffuse epileptic abnormalities. During the follow-up, seizures became drug resistant, cognitive evaluation revealed learning difficulties, and the patient complained migraine episodes. The evidence of seizure worsening before meals and the drug resistance suggested a Glut1D. Molecular analysis of SLC2A1 gene showed the presence of a pathogenic de novo mutation of the gene in heterozygosity (p.Ala275Thr, c.823G > A). Our case and the review of literature data on patients with Glut1D and absences provide a combination of clinical and EEG keys that should prompt the genetic analysis. The Glut1D should be suspected when absence seizures are associated with at least one among: irregular ictal EEG discharges, mild mental retardation, migraine, microcephaly, drug resistance, and worsening during fasting. An early diagnosis allows to establish one of the available ketogenic regimens which could modify the natural history of this treatable condition.

Electroclinical spectrum of the neuronal ceroid lipofuscinoses associated with CLN6 mutations

Objectives: To describe the clinical and neurophysiologic patterns of patients with neuronal ceroid lipofuscinoses associated with CLN6 mutations. Methods: We reviewed the features of 11 patients with different ages at onset. Results: Clinical disease onset occurred within the first decade of life in 8 patients and in the second and third decades in 3. All children presented with progressive cognitive regression associated with ataxia and pyramidal and extrapyramidal signs. Recurrent seizures, visual loss, and myoclonus were mostly reported after a delay from onset; 7 children were chairbound and had severe dementia less than 4 years from onset. One child, with onset at 8 years, had a milder course. Three patients with a teenage/adult onset presented with a classic progressive myoclonic epilepsy phenotype that was preceded by learning disability in one. The EEG background was slow close to disease onset in 7 children, and later showed severe attenuation; a photoparoxysmal response (PPR) was present in all. The 3 teenage/adult patients had normal EEG background and an intense PPR. Early attenuation of the electroretinogram was seen only in children with onset younger than 5.5 years. Somatosensory evoked potentials were extremely enlarged in all patients. Conclusions: In all patients, multifocal myoclonic jerks and seizures were a key feature, but myoclonic seizures were an early and prominent sign in the teenage/adult form only. Conversely, the childhood-onset form was characterized by initial and severe cognitive impairment coupled with electroretinogram and EEG attenuation. Cortical hyperexcitability, shown by the PPR and enlarged somatosensory evoked potentials, was a universal feature.

Comprehensive educational plan for patients with epilepsy and comorbidity (EDU-COM): a pragmatic randomised trial

Background The impact of educational strategies in the management of adverse treatment effects and drug interactions in adult patients with epilepsy with comorbidities remains undetermined. Objective The EDU-COM study is a randomised, pragmatic trial investigating the effect of a patient-tailored educational plan in patients with epilepsy with comorbidity. Methods 174 adult patients with epilepsy with chronic comorbidities, multiple-drug therapy and reporting at least one adverse treatment effect and/or drug interaction at study entry were randomly assigned to the educational plan or usual care. The primary endpoint was the number of patients becoming free from adverse treatment events and/or drug interactions after a 6-month follow-up. The number of adverse treatment events and drug interactions, health-related quality of life (HRQOL) summary score changes and the monetary costs of medical contacts and drugs were assessed as secondary outcomes. Results The primary endpoint was met by 44.0% of patients receiving the educational plan versus 28.9% of those on usual care (p=0.0399). The control group reported a significantly higher risk not to meet successfully the primary endpoint at the end of the study: OR (95% CI) of 2.29 (1.03 to 5.09). A separate analysis on drug adverse effects and drug interactions showed that the latter were more sensitive to the effect of educational treatment. Quality of life and costs were not significantly different in the two groups. Conclusions A patient-tailored educational strategy is effective in reducing drug-related problems (particularly drug interactions) in epilepsy patients with chronic comorbidities, without adding significant monetary costs. Registered at ClinicalTrials.gov, identifier NCT01804322, (http://www.clinicaltrials.gov).