Bupropion acts on multiple levels to alter brain reward circuits influenced by nicotine, in addition to reducing the expression of somatic signs of withdrawal. First, bupropion, unlike other antidepressants, increases brain reward function under baseline conditions in non-withdrawing subjects. Second, at low doses bupropion blocks the rewarding effects of nicotine. Third, bupropion reverses the negative affective aspects of nicotine withdrawal. Such actions are likely to act in concert to mediate the unique anti-smoking properties of bupropion.

KBG syndrome is a multiple congenital anomaly (MCA) syndrome comprising developmental delay, postnatal short stature, and delayed bone age. Many physical anomalies involving the face, hands, and costovertebral axis have been described in this syndrome. We present twin males with KBG syndrome and a review of 50 published case reports, with particular emphasis on the neurological aspects of KBG syndrome, including seizures, MRI findings, and behavior difficulties. It is argued that diagnostic criteria for KBG syndrome should include neurological involvement, that is, global developmental delay, seizures, and/or mental retardation (MR). The characteristic facial changes and representative hand and costovertebral anomalies are also defined. These diagnostic criteria were obtained from 50 publications and appeared to support the diagnosis in 43 cases. They will be helpful to pediatricians, geneticists, and neurologists in evaluating patients for this condition.

Increases in total nicotine dose resulted in increased severity of the affective aspects of withdrawal. Further, continuous drug exposure resulted in longer lasting withdrawal than intermittent administration even when the total nicotine dose was the same. There was no correlation between threshold elevations and somatic signs of withdrawal. In conclusion, the severity of nicotine withdrawal is mitigated by characteristics of the drug exposure regimen such as drug dose, duration of exposure and whether exposure is continuous or intermittent.

obJect Mutations in the sodium channel alpha 1 subunit gene (SCN1A) have been associated with a wide range of epilepsy phenotypes including Dravet syndrome. There currently exist few histopathological and surgical outcome reports in patients with this disease. In this case series, the authors describe the clinical features, surgical pathology, and outcomes in 6 patients with SCN1A mutations and refractory epilepsy who underwent focal cortical resection prior to uncovering the genetic basis of their epilepsy. methods Medical records of SCN1A mutation-positive children with treatment-resistant epilepsy who had undergone resective epilepsy surgery were reviewed retrospectively. Surgical pathology specimens were reviewed. results All 6 patients identified carried diagnoses of intractable epilepsy with mixed seizure types. Age at surgery ranged from 18 months to 20 years. Seizures were refractory to surgery in every case. Surgical histopathology showed evidence of subtle cortical dysplasia in 4 of 6 patients, with more neurons in the molecular layer of the cortex and white matter. conclusions Cortical resection is unlikely to be beneficial in these children due to the genetic defect and the unexpected neuropathological finding of mild diffuse malformations of cortical development. Together, these findings suggest a diffuse pathophysiological mechanism of the patients' epilepsy which will not respond to focal resective surgery. However, other authors have hypothesized that SCN1A mutations may actually protect from hippocampal sclerosis.2 Few pathological cases of Dravet syndrome have been published to date. 3,5,13,15,18 Most were case reports of autopsy specimens, and many had not undergone SCN1A testing. In this study, we review the clinical features and surgical pathology in 6 patients with treatment-resistant epilepsy who underwent surgery for intractable focal seizures and were later found to have presumed pathogenic mutations in SCN1A. We also review their outcomes and seek to draw conclusions regarding surgical evaluation and management. methodsThe medical records of 6 children with SCN1A mutations who underwent epilepsy surgery for medically refractory epilepsy were reviewed retrospectively. Patients were identified at the Children's Hospital of Philadelphia by surveying the epilepsy group to identify patients who had undergone epilepsy surgery and were later found to have SCN1A mutations. An additional patient was identified at the Cincinnati Children's Hospital. Data extracted included age at seizure onset, initial seizure types, clinical course, and neuroimaging and electroencephalography (EEG) reports. Surgical outcomes were classified using the International League Against Epilepsy (ILAE) surgical outcome scale as of their last follow-up visit. 24SCN1A mutation testing was done at commercially available laboratories (Athena and Transgenomics). A mutation was considered pathogenic if it was previously described as such, was a truncation mutation, or was a novel mutation with predicted pathogenicity (based o...

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Adrenocorticotropic hormone (ACTH), prednisone, and vigabatrin (VGB) are first-line treatments for infantile spasms (IS). 1 The antiseizure properties of VGB, an irreversible inhibitor of γ-aminobutyric acid (GABA) transaminase, are thought to emerge from increased levels of GABA. VGB can produce significant adverse effects, including irreversible visual field defects, movement disorders, and vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM). 2,3 VABAM, characterized by diffusion restriction in the globus pallidus, corpus callosum, thalamus, cerebellar dentate nuclei, midbrain, and brainstem, is reported to occur in 22%-32% of IS patients receiving VGB. 4-6 It is dose-dependent, 3 with peak discovery 3-12 months following initiation of VGB. 4,5 It is partially or completely reversed on cessation or dose reduction of VGB. 4-6 Most VABAM are asymptomatic 5 ; however, several case reports describe associated movement disorders (including choreoathetosis, myoclonus, titubation, abnormal eye movements, dystonia, opisthotonos, and tremor), dysautonomia (including bradycardia and respiratory arrest), and acute encephalopathy, together termed symptomatic VABAM. 7-12 In 2017, the International Collaborative Infantile Spasms Study (ICISS), a multicenter, randomized prospective clinical trial, demonstrated increased efficacy of combined hormonal therapy with VGB over hormonal therapy alone for IS. 13 Here, we describe three IS patients who developed symptomatic VABAM when treated contemporaneously with VGB and ACTH, characterized by encephalopathy, dyskinesias, and dysautonomia. A literature review suggests the combination of VGB with hormonal therapy (VGB-HT) is associated with fulminant symptomatic VABAM.

Survival motor neuron 1 (SMN1) gene analysis should be considered if clinical features are consistent with SMA, even if pathological or electrophysiological findings demonstrate peripheral sensorimotor polyneuropathies.

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