Cerebrospinal fluid changes following epileptic seizures unrelated to inflammation.

BACKGROUND AND PURPOSE: Analyzing cerebrospinal fluid (CSF) is crucial in the diagnostic workup of epileptic seizures to rule out autoimmunity or infections as the underlying cause. Therefore, the description of post-ictal changes in CSF is essential to differentiate between negligible and etiopathologically relevant changes in the CSF profile. METHODS: A retrospective analysis of 247 patients newly diagnosed with epileptic seizures and CSF analysis during diagnostic workup was conducted. Patients with possible or definitive autoimmune or infectious encephalitis were excluded. CSF results were evaluated for associations with seizure types, seizure etiology and electroencephalography (EEG) findings. RESULTS: An increased cell count (>4/µL) was found in 4% (n = 10), increased lactate concentration (>2.5 mmol/L) in 28% (n = 70), increased total protein (>500 mg/L) in 51% (n = 125) and a dysfunction of the blood-brain barrier in 29% (n = 71) of patients. Intrathecal immunoglobulin G production was observed in 5% (n = 12) of patients. Higher lactate concentrations were found in seizures with motor onset (P = 0.02) compared with those with non-motor onset. Patients with generalized slow activity on EEG had significantly higher lactate values (P = 0.01) and albumin quotient (P = 0.05) than those with normal EEG. CONCLUSIONS: Compared with mild pleocytosis and immunoglobulin synthesis, elevated lactate and total protein concentrations as well as blood-brain barrier dysfunction are frequently found following epileptic seizures. Our data suggest that seizure semiology might impact CSF profiles. The highest lactate concentrations were found following motor-onset seizures. Our findings may help clinicians to avoid over-interpretation of minor CSF changes; however, the exclusion of alternative causes should always be carefully considered, taking into account further clinical features.

Anti-contactin-associated protein-2 encephalitis: relevance of antibody titres, presentation and outcome.

BACKGROUND AND PURPOSE: To clarify the relevance of titres of IgG antibodies against contactin-associated protein-2 (CASPR2) in diagnosing anti-CASPR2 encephalitis and to describe features and outcomes. METHODS: This was a retrospective analysis of 64 patients with CASPR2 antibodies, categorized independently as 'autoimmune encephalitis' or 'other disease'. Logistic regression methods were performed to identify potential predictors of 'autoimmune encephalitis' in addition to CASPR2 antibodies. RESULTS: An upfront CASPR2 antibody serum titre cut-off at ≥1:200 had a diagnostic sensitivity of 85% and a specificity of 81%. Logistic regression analyses indicated that, in addition to titre, encephalitic magnetic resonance imaging (MRI) was a significant predictor of 'autoimmune encephalitis' (Nagelkerke's R2 = 0.81, P < 0.001) with high sensitivity (84%) and very high specificity (100%). Patients with CASPR2 antibodies and an estimated probability of >70% of having anti-CASPR2 encephalitis (n = 22) had limbic encephalitis (n = 18, one patient plus ataxia), Morvan syndrome (n = 2) or a hyperkinetic movement disorder (n = 2). Median modified Rankin score (mRS) at diagnosis was 3 (range 1-4). Twenty patients were male; median age was 64 (range 54-75) years; 5/15 patients with cerebrospinal fluid data had intrathecal CASPR2 antibody synthesis, and 12/19 with follow-ups >3 months (median 12 months, range 4-43 months) improved by ≥1 mRS point resulting in a median mRS of 2 (range 0-6; one death; all but one having received immunotherapy); and 2/15 patients with follow-up MRI developed hippocampal atrophy. CONCLUSIONS: Only higher CASPR2 serum antibody titres indicate anti-CASPR2 encephalitis, and diagnostic accuracy increases if MRI findings are considered. Anti-CASPR2 encephalitis has characteristic features and a favourable outcome with immunotherapy.

Diffusion tensor imaging abnormalities in photosensitive juvenile myoclonic epilepsy.

BACKGROUND AND PURPOSE: Multiple structural white matter abnormalities have been described in patients with juvenile myoclonic epilepsy (JME). In the present study, the question of whether microstructural variations exist between the two subgroups of JME, with and without photoparoxysmal responses (PPR positive and negative), was addressed using diffusion tensor imaging. METHODS: A selection of 18 patients (eight PPR positive) from a tertiary epilepsy center diagnosed with JME and 27 healthy controls was studied. The following regions of interest were investigated: the ascending reticular activating system, lateral geniculate nucleus, genu of the internal capsule, ventromedial thalamus and inferior cerebellar peduncle. RESULTS: Widespread white matter microstructural abnormalities in JME and in particular in PPR positive cases were identified. PPR positive patients demonstrated increased fractional anisotropy in the ascending reticular activating system and ventromedial thalamus compared to PPR negative patients and healthy controls. Reduced fractional anisotropy of the lateral geniculate nucleus was observed in the entire JME group compared to healthy controls. CONCLUSIONS: Several microstructural variations between PPR positive and negative JME patients have been identified. Our findings highlight the pivotal role of the thalamus in the pathophysiology of primary generalized seizures and suggest that thalamo-premotor connections are both an essential part of epileptic networks and important in the pathogenesis of photosensitivity.

Time dependency of CSF cell count, lactate and blood-CSF barrier dysfunction after epileptic seizures and status epilepticus.

BACKGROUND: This retrospective observational study was conducted to examine the temporal relationship between increased cell count, lactate concentration in cerebrospinal fluid (CSF) and blood-CSF barrier dysfunction and the onset of a seizure event. METHODS: Patients with a seizure event who underwent lumbar puncture for CSF analysis during diagnostic work-up (interindividual analysis) and those with at least one follow-up CSF analysis (intraindividual analysis) were studied. Pathologically altered parameters, such as cell count, lactate concentration, and blood-CSF barrier dysfunction as indicated by the albumin quotient (QAlb=CSF albumin/serum albumin), were examined with regard to the changes over time after seizure onset. RESULTS: An increased CSF cell count (>4/µl) was shown in 3% of our patients, whereas pathological lactate concentrations were found in 24% after single seizures and 28% after status epilepticus (SE)/recurring seizures. However, lactate levels showed a marked decrease with increasing time after an isolated seizure (p<0.0001) but not after SE/recurring seizures. Lactate levels were most frequently and significantly elevated within the first six hours after a single seizure (p<0.0001). Blood-CSF barrier dysfunction was detected in 34% after isolated seizures and in 47% after SE/recurrent seizures. Blood-CSF barrier dysfunction showed no association with latency between seizure onset and time of CSF collection. CONCLUSIONS: Changes in lactate and CSF protein concentrations are common after epileptic seizures. In contrast, CSF pleocytosis is uncommon and should prompt careful investigation for the presence of intrathecal infection or autoimmune CNS disease. Elevated lactate levels more than 6 h after the seizure event may indicate ongoing epileptic activity.

Re-review of MRI with post-processing in nonlesional patients in whom epilepsy surgery has failed.

Management of MRI-negative patients with intractable focal epilepsy after failed surgery is particularly challenging. In this study, we aim to investigate whether MRI post-processing could identify relevant targets for the re-evaluation of MRI-negative patients who failed the initial resective surgery. We examined a consecutive series of 56 MRI-negative patients who underwent resective surgery and had recurring seizures at 1-year follow-up. T1-weighted volumetric sequence from the pre-surgical MRI was used for voxel-based MRI post-processing which was implemented in a morphometric analysis program (MAP). MAP was positive in 15 of the 56 patients included in this study. In 5 patients, the MAP+ regions were fully resected. In 10 patients, the MAP+ regions were not or partially resected: two out of the 10 patients had a second surgery including the unresected MAP+ region, and both became seizure-free; the remaining 8 patients did not undergo further surgery, but the unresected MAP+ regions were concordant with more than one noninvasive modality in 7. In the 8 patients who had unresected MAP+ regions and intracranial-EEG before the previous surgery, the unresected MAP+ regions were concordant with ictal onset in 6. Our data suggest that scrutiny of the presurgical MRI guided by MRI post-processing may reveal relevant targets for reoperation in nonlesional epilepsies. MAP findings, when concordant with the patient's other noninvasive data, should be considered when planning invasive evaluation/reoperation for this most challenging group of patients.