Can developmental venous anomalies cause seizures?

Developmental venous anomalies (DVAs) are congenital anatomical variants of normal venous drainage of normal brain. Although DVAs are often discovered on the occasion of a seizure, their involvement in epilepsy is poorly studied. Our objective was to determine whether DVA can cause seizures, in the cases where there is no associated lesion, including no cavernoma or dysplasia. Based on clinical history, cerebral MRI, EEG recording, and 18F-FDG PET, we report 4 patients with DVA revealed by seizures. The first patient had a convulsive seizure caused by a hemorrhagic infarction due to thrombosis of her DVA. The second patient had a left temporo-parietal DVA next to a nonspecific lesion, possibly a sequelae of a venous infarction. The last two patients disclosed an isolated and uncomplicated DVA with a concordant epileptic focus confirmed on ictal video EEG recording. We reviewed literature and identified 21 other published cases of seizures caused by complications of a DVA and 9 patients that may have a direct link between epilepsy and an isolated and uncomplicated DVA. Seizures are linked to a DVA in two main situations: presence of an associated epileptogenic lesion, such as cavernoma or dysplasia, and occurrence of a complication of the DVA. Before concluding that a seizure is caused by a DVA, it is essential to perform full MRI protocols to search them. It remains rare and uncertain that isolated and uncomplicated DVA can cause seizures. In this last situation, physiopathological processes are probably different in each patient.

Safety of intravenous immunoglobulin in the elderly treated for a dysimmune neuromuscular disease.

INTRODUCTION: Many patients treated with intravenous immunoglobulin (IVIg) are >60 years of age. Tolerability has yet to be demonstrated in this age group. METHODS: This is a retrospective study of adverse reactions among consecutive patients treated with IVIg for neurological disorders. Risk factors were recorded. Correlation and relative risks were calculated for age, risk factors, IVIg course, daily dose, concentration, preparation, and duration of treatment. An infusion and monitoring protocol was applied. RESULTS: Two hundred forty-four patients were reviewed, including 62% who were ≥60 years of age (total dose 1.8 ± 0.4 g/kg body weight, daily dose 30.3 ± 2.0 g). Sixty-nine percent received sugar-stabilized IVIg. Forty-nine percent presented with >1 risk factor. Adverse reactions occurred in 35% and led to treatment discontinuation in 5%, with a similar incidence among age groups. In patients ≥60 years old, sucrose-free IVIg administration was an independent predictor of adverse reactions, including renal failure. CONCLUSION: In the elderly, IVIg infusions are safe. Adverse reactions mainly depend on IVIg preparation and administration. Renal failure is not uncommon with sugar-free IVIg.

A case of homocystinuria due to CBS gene mutations revealed by cerebral venous thrombosis.

BACKGROUND: Homocystinuria caused by cystathionine beta synthase (CBS) deficiency is most often diagnosed in childhood and has a variable expressivity. The most frequent abnormalities include intellectual disability, ectopia lentis, myopia, skeletal abnormalities or thromboembolism. OBJECTIVE: To report a case of homocystinuria unraveled by cerebral venous thrombosis (CVT). OBSERVATION: A 17 year old female was admitted in our department of neurology for subacute headache and presented seizures in the emergency room. Cerebral imaging revealed CVT. Severe hyperhomocysteinemia was found and led to the diagnosis of homocystinuria due to composite heterozygous mutations in the CBS gene. Further investigations disclosed lens subluxation in association with myopia, mild scoliosis and osteopenia. The patient was treated by heparin followed by warfarin, vitamin therapy and dietary methionine restriction. Total homocysteine and methionine levels became normal in a few weeks and the patient had a complete recovery. CONCLUSION: In patients with CVT, plasma total homocysteine measurement as part of the etiologic work up may reveal severe hyperhomocysteinemia due to CBS or remethylation defects that require specific treatment and management including perhaps protein-restricted diet and/or vitamin therapy for life.

Efficacy of the histamine 3 receptor (H3R) antagonist pitolisant (formerly known as tiprolisant; BF2.649) in epilepsy: dose-dependent effects in the human photosensitivity model.

A new class of drugs, the nonimidazole histamine 3 receptor (H3R) antagonists, has been developed in the past decade for treatment of various brain diseases. Pitolisant is such a drug. We studied the pharmacodynamic effect of pitolisant in patients with epilepsy in early Phase II, using the photosensitivity proof of concept model. A total of 14 adult patients (11 females and 3 males; 5 drug naïve) were studied for three days to evaluate the effect of a single oral dose of pitolisant on EEG photosensitivity ranges. All patients showed repeatedly a generalized photoparoxysmal response (PPR) prior to drug administration on placebo Day 1. A statistically significant suppressive effect (standardized photosensitive response [SPR] reduction as measured with paired t-tests) for 20-, 40-, or 60-mg doses of pitolisant was seen in 9/14 (64%) patients of whom 6/14 (43%) showed abolition of the response to intermittent photic stimulation (IPS). Patients on the highest dosage (60 mg) showed the strongest effect with an effect lasting up to 28 h. Thus, full-scale Phase II studies with this novel H3R antagonist, pitolisant, in patients with epilepsy are warranted.

Cortical border-zone infarcts: clinical features, causes and outcome.

OBJECTIVE: To report the clinical features, causes and outcome of cerebral cortical border-zone infarcts BZI (C-BZI). METHODS: The authors prospectively included patients with MRI-confirmed C-BZI among individuals consecutively admitted in Stroke Unit. RESULTS: Forty-five patients presented C-BZI out of 589 with MRI-confirmed cerebral infarcts (7.6%). Particular clinical characteristics existed in C-BZI in comparison with other cerebral infarctions as a whole, including: (1) frequent transient symptoms at onset (27% vs 9%; p<0.001) and low severity score (NIHSS=3.1±3.0 vs 5.2±6.1; p=0.02); (2) early seizures in first 2 weeks (7/45 (15.6%) vs 12/544 (2.2%); p<0.001), even when focusing only on other infarctions involving the cerebral cortex (15.6% vs 4.3%; p<0.01); (3) heterogeneous clinical presentation but specific transcortical aphasia allowing a clinical suspicion of BZI before MRI; and (4) frequently associated internal carotid disease (69%), with subsequent early surgery in 75% of the cases. Following adapted care in stroke unit, C-BZIs' prognosis appeared good (Rankin score ≤2 at D90) for 82% of the patients. CONCLUSION: Some clinical features are overrepresented in such infarctions, including initial transient symptoms preceding the onset of a completed deficit, transcortical aphasia and early seizures. Despite lower initial severity, C-BZIs justify early management in stroke unit, often followed by carotid surgery, leading to an overall good prognosis.

Watershed infarctions are more prone than other cortical infarcts to cause early-onset seizures.

BACKGROUND: Early-onset seizures(ESs) have been reported in 2% to 6% of strokes. Most previous studies have been retrospective and did not systematically perform cerebral magnetic resonance imaging (MRI). OBJECTIVE: To determine the prevalence and determinants of ESs in a prospective cohort. DESIGN: Prospective cohort study. SETTING: Stroke unit in an academic hospital. PATIENTS: Six hundred sixty-one consecutive individuals admitted to our stroke unit during an 18-month period for suspected stroke. MAIN OUTCOME MEASURES: Initial investigations systematically included cerebral MRI. Among patients with MRI-confirmed cerebral infarction, individuals with ES, defined as occurring within 14 days of stroke, were identified. RESULTS: Three hundred twenty-eight patients had MRI-confirmed cerebral infarcts and 178 had cortical involvement. The ESs, all initially partial seizures, occurred in 14 patients (4.3%) and at stroke onset in 5 patients. The ESs occurred exclusively in patients with cortical involvement (P <.001). With infarcts involving the cerebral cortex, there was a higher risk of ESs in watershed infarctions than in territorial strokes (6 of 26 [23.1%] vs 8 of 152 [5.3%], P = .007). Logistic regression analysis showed an almost 4-fold increased risk of ES in patients with watershed infarctions compared with other cortical infarcts (odds ratio, 4.7; 95% confidence interval, 1.5- 15.4; P = .01). Age, sex, diabetes mellitus, hypertension, smoking, National Institutes of Health Stroke Scale score, and cardioembolic origin were not significant risk factors for ES. CONCLUSIONS: The cortical hemispheric location of ischemic strokes is associated with a higher risk of ES. Among these patients, the watershed mechanism is a strong and independent determinant of stroke-related ES.

Symptomatic paroxysmal dysarthria-ataxia in demyelinating diseases.

Paroxysmal dysarthria-ataxia syndrome (PDA) is a rare neurological disorder that can be either primary or symptomatic of acute neurological dysfunction. Episodes of symptomatic PDA are poorly documented and there are no video reports. We describe the cases of two patients with symptomatic PDA related to demyelinating diseases. Detailed studies of the patients' speech disorders showed that the dysarthria and gait disorders were of the ataxic type in both cases. Both patients had midbrain lesions at or below the level of the red nucleus, confirming that this area is critically involved in PDA. The best clinical signs for distinguishing between symptomatic and primary PDA are adult onset and short (<1 min) episodes in the former. If these signs are present, brain MRI should be used to identify a cause of symptomatic PDA.

Pilomotor seizures associated with sequential changes in magnetic resonance imaging.

Piloerection is rarely described in seizures. This symptom has been most frequently observed in patients with temporal lobe epilepsy and is rarely the principal clinical feature of seizures. No specific etiology of epilepsy associated with pilomotor seizures has been reported. We present the first case of a patient who experienced sudden and transitory epilepsy with pilomotor seizures occurring several times a day for months, and associated with sequential changes of the left hippocampus demonstrated by magnetic resonance imaging. [Published with video sequences].

Clinical analysis in familial cortical myoclonic tremor allows differential diagnosis with essential tremor.

Familial cortical myoclonic tremor (FCMT) is a rare disorder often leading to a wrong clinical diagnosis of essential tremor. Electrophysiological data are usually considered to allow a correct diagnosis. We describe a FCMT French family with previously unreported clinical features such as sensitivity to glucose deprivation, vibration, repetitive visual patterns, and intense visual or auditory stimulation and contrasts. Electrophysiological studies of the propositus confirm the cortical reflex myoclonus elicited by photic stimulation and the absence of epileptic electroencephalographic discharges. We emphasize that a precise clinical analysis can lead to a correct diagnosis before electrophysiological confirmation. This is also the first-ever report of efficacy of levetiracetam in FCMT.

Fulminant hepatitis after grand mal seizures: mechanisms and role of liver transplantation.

Fulminant liver failure is a rare complication of grand mal seizures with a high mortality, the prognosis being largely determined by the combination of the hepatic and neurologic insults. The mechanisms of acute liver failure secondary to grand mal epilepsy and the place of liver transplantation in this context are poorly defined and are the subject of this report. A series of 6 such patients is presented. All had a history of chronic primary or post-traumatic epilepsy and presented with acute liver failure shortly after a grand mal fit. Detailed accounts of background, presentation, and management are given and integrated with blood, radiologic, and histologic investigations. Two of the 6 patients survived, 1 making a full recovery and the other with neurologic sequelae. Two patients underwent liver transplantation but died with severe neurologic sequelae despite improving liver function. The remaining 2 patients were considered too ill to undergo liver transplantation and died in multiple organ failure. Liver histology from needle biopsy and/or native liver explants identified lesions compatible with a combination of steatosis and necrosis. Factor V and transaminase levels may allow early identification of patients in whom liver function is likely to improve spontaneously. In conclusion, the mechanisms of liver failure occurring after grand mal seizures appear multifactorial, including hypoxia, steatosis, and drug-induced components. The neurological prognosis and overall survival of these patients remains poor.

[True or pseudo epilepsy in the adult]. / Vraie ou fausse épilepsie chez l'adulte.

THE EXTENT OF THE PROBLEM: A patient can be misleadingly considered as epileptic although he is not. Conversely an epileptic man not be recognised as such. Moreover, in some patients epilepsy seizures may co-exist with pseudo-seizures. THE PROBLEMS IN DIAGNOSIS: Each stage of the diagnosis of epilepsy is limited, whether regarding anamnesis, electroencephalogram, not only standard but also video, or even the semiological analysis because of the clinical polymorphism of partial epileptic seizures. THE MAJOR DIFFERENTIAL DIAGNOSES: Migraine with aura may be difficult to differentiate from occipital attacks with visual hallucinations. Bilateral tonic or chronic phenomena may occur during syncope. A partial epileptic seizure may simulate a cerebral vascular stroke. Paroxistic anxiety (panic attacks) can resemble that observed during partial seizures with vegetative semiology. In fact the problem is dominated by the pseudo-epileptic seizures, the diagnosis of which is evoked on the clinical aspect, the mode of onset, the past history of the patient and confirmed by simultaneous EEG video recording. FROM A THERAPEUTIC POINT OF VIEW: The best action is preventive. It consists in the earliest possible detection of the pseudo-epileptic seizures and in avoiding so-called 'test' treatments.