Hemimegalencephaly with Bannayan‐Riley‐Ruvalcaba syndrome

Hemimegalencephaly is known to occur in Proteus syndrome, but has not been reported, to our knowledge, in the other PTEN mutation‐related syndrome of Bannayan‐Riley‐Ruvalcaba. Here, we report a patient with Bannayan‐Riley‐Ruvalcaba syndrome who also had hemimegalencephaly and in whom the hemimegalencephaly was evident well before presentation of the characteristic manifestations of Bannayan‐Riley‐Ruvalcaba syndrome. An 11‐year‐old boy developed drug‐resistant focal seizures on the fifth day of life. MRI revealed left hemimegalencephaly. He later showed macrocephaly, developmental delay, athetotic quadriplegic cerebral palsy, and neuromuscular scoliosis. Freckling of the penis, which is characteristic of Bannayan‐Riley‐Ruvalcaba syndrome, was not present at birth but was observed at 9 years of age. Gene analysis revealed a c.510 T>G PTEN mutation. This patient and his other affected family members, his father and two siblings, were started on the tumour screening procedures recommended for patients with PTEN mutations. This case highlights the importance of early screening for PTEN mutations in cases of hemimegalencephaly not otherwise explained by another disorder, even in the absence of signs of Proteus syndrome or the full manifestations of Bannayan‐Riley Ruvalcaba syndrome.     

A primigravida with very‐long‐chain acyl‐CoA dehydrogenase deficiency

Introduction: Valosin‐containing protein (VCP) is a ubiquitously expressed, multifunctional AAA‐ATPase protein. Its dominant mutations cause hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD) or amyotrophic lateral sclerosis. The pattern of muscle weakness in IBMPFD patients is variable and includes limb‐girdle, scapuloperoneal, distal, or axial distributions. Case Report: We report a 63‐year‐old man with progressive scapuloperoneal weakness, head drop, and hyperCKemia since age 40 years. Electromyography showed myopathic changes and rare myotonic discharges. Muscle biopsy revealed numerous lobulated fibers, few fibers with glycogen accumulation, and rare fibers with polyglucosan bodies. Rimmed vacuoles and congophilic inclusions, often seen in IBMPFD, were absent. VCP sequencing identified a novel heterozygous c. 1160G>A mutation resulting in p.Asn387Ser substitution. Conclusions: Our patient broadens the pathological spectrum of VCP‐myopathy and emphasizes the importance of VCP analysis in patients with scapuloperoneal muscular dystrophy despite the absence of Paget disease, dementia, rimmed vacuoles, or intracellular amyloid deposition. Muscle Nerve 50:295–299, 2014     

Adult‐onset drug‐refractory seizure disorder associated with anti–voltage‐gated potassium‐channel antibody

Voltage‐gated potassium channels are widely expressed throughout the entire nervous system. These channels play a critical role in establishing the resting membrane potential and generation of neuronal action potentials. There is mounting evidence that autoantibodies reactive to neuronal cell surface antigens, such as voltage‐gated potassium channels, play a pathogenic role in a wide spectrum of central and peripheral nervous system disorders. We report a case of new‐onset drug‐refractory seizure disorder associated with the presence of high levels of serum anti–voltage‐gated potassium channel antibodies that responded only to immunotherapy. As demonstrated by this case report, anti–voltage‐gated potassium channel antibody associated drug‐refractory seizure disorder, although rare, should be considered in patients with unexplained adult‐onset seizure activity. Once the diagnosis has been established the initiation of immunotherapy should be undertaken without delay.     

Mowat‐Wilson syndrome presenting with fever‐associated seizures

Mowat‐Wilson syndrome (MWS) is a disorder caused by mutations or deletions of the zinc finger E‐box‐binding homeobox 2 (ZEB2) gene. Diagnosis of MWS can be challenging to neurologists, because its manifestations are diverse and the spectrum of genetic mutations are broad. Here, we describe two patients with MWS who initially showed atypical forms of fever‐triggered seizures during childhood. Both had characteristic facial features, cognitive impairment, and genito‐urinary anomalies consistent with MWS. By performing targeted next‐generation sequencing (NGS) using a gene panel for epilepsy, we were able to identify a nonsense mutation (c.1965C>A) in the ZEB2 gene of one patient and a frameshift mutation (c.2348dupC) in the other patient. Fever‐induced seizures can be presenting signs of MWS. MWS should be considered in the differential diagnosis of fever‐induced seizures, especially when the patient has distinctive facial features and multiple anomalies, including cardiac, genito‐urinary, and eye defects.     

Dermatomyositis‐like muscle pathology in patients with chronic graft‐versus‐host disease

Myositis is a rare complication of chronic graft‐versus‐host disease (cGVHD) following hematopoietic stem cell transplantation (HSCT). Almost all such patients have been reported to have polymyositis (PM). We describe clinical, pathologic, and molecular studies of 3 patients with cGVHD following allogeneic HSCT who developed myopathy. In each case, perifascicular atrophy, the pathognomonic histologic feature of dermatomyositis (DM), was observed. Muscle Nerve, 2009     

Bacillus Calmette‐Guerin vaccine‐mediated neuroprotection is associated with regulatory T‐cell induction in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mouse model of Parkinson's disease

We previously showed that, in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD), vaccination with bacillus Calmette‐Guerin (BCG) prior to MPTP exposure limited the loss of striatal dopamine (DA) and dopamine transporter (DAT) and prevented the activation of nigral microglia. Here, we conducted BCG dose studies and investigated the mechanisms underlying BCG vaccination's neuroprotective effects in this model. We found that a dose of 1 × 10⁶ cfu BCG led to higher levels of striatal DA and DAT ligand binding (28% and 42%, respectively) in BCG‐vaccinated vs. unvaccinated MPTP‐treated mice, but without a significant increase in substantia nigra tyrosine hydroxylase‐staining neurons. Previous studies showed that BCG can induce regulatory T cells (Tregs) and that Tregs are neuroprotective in models of neurodegenerative diseases. However, MPTP is lymphotoxic, so it was unclear whether Tregs were maintained after MPTP treatment and whether a relationship existed between Tregs and the preservation of striatal DA system integrity. We found that, 21 days post‐MPTP treatment, Treg levels in mice that had received BCG prior to MPTP were threefold greater than those in MPTP‐only‐treated mice and elevated above those in saline‐only‐treated mice, suggesting that the persistent BCG infection continually promoted Treg responses. Notably, the magnitude of the Treg response correlated positively with both striatal DA levels and DAT ligand binding. Therefore, BCG vaccine‐mediated neuroprotection is associated with Treg levels in this mouse model. Our results suggest that BCG‐induced Tregs could provide a new adjunctive therapeutic approach to ameliorating pathology associated with PD and other neurodegenerative diseases. © 2013 Wiley Periodicals, Inc.