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CACNA1A deletions cause epilepsy, ataxia, and a range of neurocognitive deficits, including inattention, impulsivity, intellectual deficiency and autism. To investigate the underlying mechanisms, we generated mice carrying a targeted Cacna1a deletion restricted to parvalbumin-expressing (PV) neurons (PV Cre ;Cacna1a c/+ ) or to cortical pyramidal cells (PC) (Emx1 Cre ;Cacna1a c/+ ). GABA release from PV-expressing GABAergic interneurons (PV-INs) is reduced in PV Cre ;Cacna1a c/+ mutants, resulting in impulsivity, cognitive rigidity and inattention. By contrast, the deletion of Cacna1a in PCs does not impact cortical excitability or behaviour in Emx1 Cre ;Cacna1a c/+ mutants. A targeted Cacna1a deletion in the orbitofrontal cortex (OFC) results in reversal learning deficits while a medial prefrontal cortex (mPFC) deletion impairs selective attention. These deficits can be rescued by the selective chemogenetic activation of cortical PV-INs in the OFC or mPFC of PV Cre ;Cacna1a c/+ mutants. Thus, Cacna1a haploinsufficiency disrupts perisomatic inhibition in frontal cortical circuits, leading to a range of potentially reversible neurocognitive deficits., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

As part of a presurgical investigation for a resection of a tumor located in the left temporal brain region, we evaluated pre- and postsurgical language lateralization in a right-handed boy with refractory epilepsy. In this study, we compared functional near infrared spectroscopy (fNIRS) results obtained while the participant performed expressive and receptive language tasks with those obtained using functional magnetic resonance imaging (fMRI). This case study illustrates the potential for NIRS to contribute favorably to the localization of language functions in children with epilepsy and cognitive or behavioral problems and its potential advantages over fMRI in presurgical assessment. Moreover, it suggests that fNIRS is sensitive in localizing an atypical language network or potential brain reorganization related to epilepsy in young patients.

CACNA1A loss-of-function mutations classically present as episodic ataxia type 2 (EA2), with brief episodes of ataxia and nystagmus, or with progressive spinocerebellar ataxia (SCA6). A minority of patients carrying CACNA1A mutations develops epilepsy. Non-motor symptoms associated with these mutations are often overlooked. In this study, we report 16 affected individuals from four unrelated families presenting with a spectrum of cognitive impairment including intellectual deficiency, executive dysfunction, ADHD and/or autism, as well as childhood-onset epileptic encephalopathy with refractory absence epilepsy, febrile seizures, downbeat nystagmus and episodic ataxia. Sequencing revealed one CACNA1A gene deletion, two deleterious CACNA1A point mutations including one known stop-gain and one new frameshift variant and a new splice-site variant. This report illustrates the phenotypic heterogeneity of CACNA1A loss-of-function mutations and stresses the cognitive and epileptic manifestations caused by the loss of CaV2.1 channels function, presumably affecting cerebellar, cortical and limbic networks.

Although children with epilepsy tend to exhibit more reading difficulties than their classmates, no systematic studies have investigated the relationship between these difficulties and epilepsy. As functional neuroimaging studies have implicated both temporal and frontal lobes in the phonological aspect of reading [K.R. Pugh, B.A. Shaywitz, S.E. Shaywitz, et al. Brain 1996;119:1221-38], seizure activity originating in either region could interfere with phonological processing, whereas generalized seizures would not disturb this function as much. To explore this hypothesis, we compared the metaphonological skills of school-aged children with either temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), or generalized absence seizures (ABS) with those of healthy controls. While the reading ability of all epileptic children was close to 2 years behind expectations, children with TLE did not differ from the controls on phonological tasks. In contrast, children with FLE exhibited significant deficits, whereas children with ABS showed difficulties restricted to phonemic segmentation. The results suggest that FLE and, to a lesser extent, generalized seizures may interfere with phonological processing, whereas TLE may affect other aspects of reading.

An epizootic of bovine mastitis caused by a nontuberculous mycobacterial agent occurred in a large Quebec dairy herd. This mastitis problem was characterized by the occurrence of a high number of cows with severely inflamed, indurated and therapeutically incurable quarters. Routine diagnostic laboratory methods yielded negative cultural findings. Approximately 40% of the milking cows developed chronic mastitis. Poor sanitation, improper milking procedures and a faulty milking system prevailed at that time.