Mentalis muscle related reflexes.

The mentalis muscle (MM) arises from the incisive fossa of the mandible, raises and protrudes the lower lip. Here, we aim to characterize responses obtained from MM by supraorbital and median electrical as well as auditory stimuli in a group of 16 healthy volunteers who did not have clinical palmomental reflex. Reflex activities were recorded from the MM and orbicularis oculi (O.oc) after supraorbital and median electrical as well as auditory stimuli. Response rates over MM were consistent after each stimulus, however, mean latencies of MM response were longer than O.oc responses by all stimulation modalities. Shapes and amplitudes of responses from O.oc and MM were similar. Based on our findings, we may say that MM motoneurons have connections with trigeminal, vestibulocochlear and lemniscal pathways similar to other facial muscles and electrophysiological recording of MM responses after electrical and auditory stimulation is possible in healthy subjects.

Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration.

Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific de-ubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfuction, and spasticity with upper motor neuron dysfunction. Through homozygosity mapping of the affected individuals followed by whole-exome sequencing of the index case, we identified a previously undescribed homozygous missense mutation within the ubiquitin binding domain of UCHL1 (UCHL1(GLU7ALA)), shared by all affected subjects. As demonstrated by isothermal titration calorimetry, purified UCHL1(GLU7ALA), compared with WT, exhibited at least sevenfold reduced affinity for ubiquitin. In vitro, the mutation led to a near complete loss of UCHL1 hydrolase activity. The GLU7ALA variant is predicted to interfere with the substrate binding by restricting the proper positioning of the substrate for tunneling underneath the cross-over loop spanning the catalytic cleft of UCHL1. This interference with substrate binding, combined with near complete loss of hydrolase activity, resulted in a >100-fold reduction in the efficiency of UCHL1(GLU7ALA) relative to WT. These findings demonstrate a broad requirement of UCHL1 in the maintenance of the nervous system.

A novel GJC2 mutation associated with hypomyelination and Müllerian agenesis syndrome: coincidence or a new entity?

In recent years, several new white matter diseases have been identified based on magnetic resonance imaging and clinical findings. For most newly defined disorders the genetic basis has been identified. However, there is still a large group of patients without a specific diagnosis. Hypomyelinating leukodystrophies are the largest group among them. In some disorders characterized by hypomyelination only central nervous system involvement is observed, but in some disorders involvement of other organs is observed as well, such as eyes or teeth. Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating disorder of the central nervous system characterized by nystagmus, ataxia, and progressive spasticity. The disease is caused by mutations in GJC2, the gene that encodes the gap junction protein connexin 47. Here we describe hypomyelination and Müllerian agenesis syndrome in a girl who is homozygous for a novel mutation in the GJC2 gene. It is an open question whether this is an association by chance or a feature of PMLD not previously noted.

Challenges in diagnosing SSPE.

PURPOSE: The typical clinical presentation of subacute sclerosing panencephalitis (SSPE) includes behavioral and intellectual changes followed by myoclonia. However, there are a considerable number of SSPE cases which present with distinct clinical features that can lead to a diagnostic difficulty. In this report, we summarize the clinical features of patients with SSPE who have uncommon presentations or features of the disease or coexisting medical conditions which may lead to diagnostic difficulties. METHODS: We studied 173 patients, all under the age of 17. Patients were included in the study group according to following criteria: onset of the disease before age 2 years, seizures occurring before the onset of myoclonia and/or behavioral symptoms, extrapyramidal or cerebellar signs and ocular manifestations as initial presenting symptoms, fulminant course including coma or death within 6 months. Additionally, patients with onset of SSPE at the setting of a known neurological disorder are defined as another group in the study. RESULTS: Out of 173 patients with SSPE who were followed in two neurology centers, 31 (17.9%) met our criteria. CONCLUSIONS: We found a relative high frequency of these clinical features. Our findings suggest that clinicians should be aware of this clinical characteristics and rule out the disease in cases were other common causes have been excluded, especially in countries with insufficient measles immunization.

Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy.

Congenital ataxia with cerebellar hypoplasia is a heterogeneous group of disorders that presents with motor disability, hypotonia, incoordination, and impaired motor development. Among these, disequilibrium syndrome describes a constellation of findings including non-progressive cerebellar ataxia, mental retardation, and cerebellar hypoplasia following an autosomal recessive pattern of inheritance and can be caused by mutations in the Very Low Density Lipoprotein Receptor (VLDLR). Interestingly, while the majority of patients with VLDL-associated cerebellar hypoplasia in the literature use bipedal gait, the previously reported patients of Turkish decent have demonstrated similar neurological sequelae, but rely on quadrupedal gait. We present a consanguinous Turkish family with two siblings with cerebellar atrophy, predominantly frontal pachygyria and ataxic bipedal gait, who were found to have a novel homozygous deletion in the VLDLR gene identified by using high-density single nucleotide polymorphism microarrays for homozygosity mapping and identification of CNVs within these regions. Discovery of disease causing homozygous deletions in the present Turkish family capable of maintaining bipedal movement exemplifies the phenotypic heterogeneity of VLDLR-associated cerebellar hypoplasia and ataxia.

Startle and blink reflex in high functioning autism.

An important clinical feature of autism is the presence of atypical responses to sensory stimuli. In this study, we investigated if high functioning autistic patients had abnormalities in the blink reflex and the startle reaction to auditory or somatosensory stimuli. Fourteen patients aged between 7 and 16 years were included in the study. We found a longer latency of the blink reflex, an increased duration and amplitude of the auditory startle reaction and a lower presence rate of the somatosensorial startle reaction in autistic patients. To better define the sensorial characteristics of the disease could improve the therapeutic management of children with autism spectrum disorder.

Epilepsy Surgery in Children with Lesional Partial Epilepsies.

AIM: Surgery for epilepsy is a significant treatment alternative with favorable outcomes in the pediatric age group. In this study we present the surgical outcomes of pediatric population referred to our center. MATERIAL AND METHODS: The clinical data of 126 patients (≤18 years) with lesional partial epilepsies operated in our center between 1995- 2011 were evaluated retrospectively. Parameters investigated were gender, age at seizure onset, duration of epilepsy, etiology, type and location of operation and outcome. Seizure outcome was classified according to Engel's classification. RESULTS: The study group consisted of 70 males (55,6%) and 56 females (44.4%). The most common etiology was malformation of cortical development followed by tumors and hippocampal sclerosis. Overall 73.8% of patients had Engel I, 13.5% Engel II and 11.9% Engel III+IV postoperative seizure outcome. CONCLUSION: The results of our pediatric patients who underwent surgery were similar to previous reports in the literature. The seriousness of the clinical picture should tempt physicians to refer the patients as soon as possible to avoid long term complications like epileptic encephalopathies and the side effects of antiepileptic drugs during the development of the young brains.

Hypomyelination and congenital cataract: broadening the clinical phenotype.

OBJECTIVE: To further delineate the clinical spectrum of hypomyelination and congenital cataract (HCC), a rare autosomal recessive white matter disorder due to deficiency of a membrane protein, hyccin, encoded by FAM126A. DESIGN: Case reports and literature review. SETTING: University hospital. PATIENTS: Nine additional patients with HCC. RESULTS: Cataract was congenital in 5 patients; it was found at 4, 5, and 7 months in 3 patients, and only a mild lens opacity was noted at age 3 years in the remaining patient. Neurologic presentation was at birth in 1 child, was characterized by developmental delay at the end of the first year of life in 7 patients, and was characterized by sudden motor regression in the second year of life in the remaining patient. Three patients were able to walk with support only, 5 achieved the ability to walk without support, and the remaining patient was not able to stand at age 2 years. Mental retardation was present in all patients. Peripheral neuropathy was present in the 8 patients who underwent neurophysiological investigations. Brain magnetic resonance imaging showed hypomyelination associated with periventricular white matter abnormalities in all patients and brainstem pyramidal tract involvement in 8. Molecular analysis depicted 3 novel mutations and the previously reported IVS5 + 1G>T mutation. CONCLUSIONS: Our study broadens the clinical spectrum of HCC. The clinical variability ranges from severe early-onset neurologic impairment to a milder phenotype. In contrast to this clinical variability, the peculiar magnetic resonance pattern of hypomyelination combined with increased periventricular white matter water content allows distinction of HCC from other forms of hypomyelinating leukoencephalopathies.

Efficacy of nebivolol and amitriptyline in the prophylaxis of cyclic vomiting syndrome: a case report.

BACKGROUND: Cyclic vomiting syndrome (CVS) is an episodic disorder with recurrent attacks of nausea and vomiting. The exact cause of the disorder is still unclear. It was first described in children but may affect patients of any age. The syndrome is frequently misdiagnosed, and patients receive redundant investigations and treatments. Patients are referred finally to a neurologist because of the differential diagnosis of abdominal migraine or abdominal epilepsy. CASE REPORT: We present a 18-year-old girl with episodic nausea and vomiting attacks who was diagnosed as CVS. The attacks regressed with combination treatment with amitriptyline and nebivolol. CONCLUSION: CVS has no specific diagnostic test and the diagnosis is based on history, clinical presentation and exclusion of other possible causes with similar presentation. The syndrome has a strong association with migraine; treatment options may also overlap. Treatment is still based on case series and reports. Here, we aim to present the clinical features as well as treatment response of a patient with CVS.

Four novel SCN1A mutations in Turkish patients with severe myoclonic epilepsy of infancy (SMEI).

Severe myoclonic epilepsy of infancy (SMEI) (OMIM #607208), also known as Dravet syndrome, is a rare genetic disorder characterized by frequent generalized, unilateral clonic or tonic-clonic seizures that begin during the first year of life. Heterozygous de novo mutations in the SCN1A gene, which encodes the neuronal voltage-gated sodium channel α subunit type 1 (Nav1.1), are responsible for Dravet syndrome, with a broad spectrum of mutations and rearrangements having been reported. In this study, the authors present 4 novel mutations and confirm 2 previously identified mutations in the SCN1A gene found in a cohort of Turkish patients with Dravet syndrome. Mutational analysis of other responsible genes, GABRG2 and PCDH19, were unrevealing. The authors' findings add to the known spectrum of mutations responsible for this disease phenotype and once again reinforce our understanding of the allelic heterogeneity of this disease.