Nitrous oxide-induced motor-predominant axonal peripheral neuropathy: A phenotype distinct from isolated vitamin B12 deficiency

Highlights: N2O toxicity and B12 deficiency both cause a sensory predominant myeloneuropathy. N2O abuse may also lead to a selectively severe motor axonal peripheral neuropathy. This motor neuropathy phenotype may be related to N2O direct neural toxicity. In-vivo measures of motor axonal dysfunction are more pronounced in N2O abuse

Mitochondrial Neurogastrointestinal Encephalomyopathy: Into the Fourth Decade, What We Have Learned So Far.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare metabolic autosomal recessive disease, caused by mutations in the nuclear gene TYMP which encodes the enzyme thymidine phosphorylase. The resulting enzyme deficiency leads to a systemic accumulation of the deoxyribonucleosides thymidine and deoxyuridine, and ultimately mitochondrial failure due to a progressive acquisition of secondary mitochondrial DNA (mtDNA) mutations and mtDNA depletion. Clinically, MNGIE is characterized by gastrointestinal and neurological manifestations, including cachexia, gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, ophthalmoplegia and ptosis. The disease is progressively degenerative and leads to death at an average age of 37.6 years. As with the vast majority of rare diseases, patients with MNGIE face a number of unmet needs related to diagnostic delays, a lack of approved therapies, and non-specific clinical management. We provide here a comprehensive collation of the available knowledge of MNGIE since the disease was first described 42 years ago. This review includes symptomatology, diagnostic procedures and hurdles, in vitro and in vivo disease models that have enhanced our understanding of the disease pathology, and finally experimental therapeutic approaches under development. The ultimate aim of this review is to increase clinical awareness of MNGIE, thereby reducing diagnostic delay and improving patient access to putative treatments under investigation

Different attachment styles correlate with mood disorders in adults with epilepsy or migraine.

PURPOSE: Interpersonal relationships are viewed as important contexts within which psychopathology emerges and persists or desists. Attachment theory describes the dynamics of long-term relationships between humans especially in families and lifelong friendships. The present study was aimed at investigating attachment styles in adult patients with epilepsy as compared to subjects with migraine and their potential correlates with a history of mood disorders. METHODS: A consecutive sample of 219 adult outpatients with epilepsy (117) or migraine (102) was assessed with the Attachment Style Questionnaire (ASQ). RESULTS: Patients with epilepsy and a lifetime history of mood disorders presented elevated scores for Need for approval (p<0.001) and Preoccupation with relationships (p<0.001). Age correlated with the Relationships as secondary (r=0.322; p<0.001) and Need for approval (r=0.217; p=0.019) subscales while age at onset correlated only with Relationships as secondary (r=0.225; p=0.015). Seizure-free patients presented lower scores for Need for approval (p=0.003). Patients with migraine and a lifetime history of mood disorders presented lower scores in Confidence (p=0.002) and higher scores in Discomfort with closeness (p=0.026). CONCLUSIONS: An anxious-preoccupied attachment correlated with mood disorders in epilepsy while it was an avoidant pattern in migraine. Our results bring further data on the role of psychological variables in mood disorders in epilepsy. Further studies will allow early identification of patients at risk and the development of preventive strategies

De novo single-nucleotide and copy number variation in discordant monozygotic twins reveals disease-related genes

Recent studies have demonstrated genetic differences between monozygotic (MZ) twins. To test the hypothesis that early post-twinning mutational events associate with phenotypic discordance, we investigated a cohort of 13 twin pairs (n = 26) discordant for various clinical phenotypes using whole-exome sequencing and screened for copy number variation (CNV). We identified a de novo variant in PLCB1, a gene involved in the hydrolysis of lipid phosphorus in milk from dairy cows, associated with lactase non-persistence, and a variant in the mitochondrial complex I gene MT-ND5 associated with amyotrophic lateral sclerosis (ALS). We also found somatic variants in multiple genes (TMEM225B, KBTBD3, TUBGCP4, TFIP11) in another MZ twin pair discordant for ALS. Based on the assumption that discordance between twins could be explained by a common variant with variable penetrance or expressivity, we screened the twin samples for known pathogenic variants that are shared and identified a rare deletion overlapping ARHGAP11B, in the twin pair manifesting with either schizotypal personality disorder or schizophrenia. Parent-offspring trio analysis was implemented for two twin pairs to assess potential association of variants of parental origin with susceptibility to disease. We identified a de novo variant in RASD2 shared by 8-year-old male twins with a suspected diagnosis of autism spectrum disorder (ASD) manifesting as different traits. A de novo CNV duplication was also identified in these twins overlapping CD38, a gene previously implicated in ASD. In twins discordant for Tourette's syndrome, a paternally inherited stop loss variant was detected in AADAC, a known candidate gene for the disorder

Change of pitch due to carbamazepine and oxcarbazepine independently

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Introduction; Absolute pitch (AP) is the term used to denote the cognitive ability to spontaneously and effortlessly identify and vocally produce specific musical tones without a reference note.1 Abnormalities of pitch perception are a recognized rare side effect of carbamazepine (CBZ). The mechanism of this side effect is not clear. The same symptom may also be associated with oxcarbazepine (OXC) although this is even rarer. We report a twenty-two year-old woman with partial and prolonged secondarily generalized seizures who complained of a one semitone lowering of pitch perception during CBZ therapy. After stopping CBZ and switching to OXC, she noticed that pitch perception was one semitone higher than normal.Absolute pitch (AP) is the term used to denote the cognitive ability to spontaneously and effortlessly identify and vocally produce specific musical tones without a reference note. Abnormalities of pitch perception are a recognized rare side effect of carbamazepine (CBZ). The mechanism of this side effect is not clear. The same symptom may also be associated with oxcarbazepine (OXC) although this is even rarer. We report a twenty-two year-old woman with partial and prolonged secondarily generalized seizures who complained of a one semitone lowering of pitch perception during CBZ therapy. After stopping CBZ and switching to OXC, she noticed that pitch perception was one semitone higher than normal