Early impairment of somatosensory evoked potentials in very young children with achondroplasia with foramen magnum stenosis.

AIM: To evaluate the contribution of somatosensory evoked potentials after median nerve (MN-SEPs) and posterior tibial nerve (PTN-SEPs) stimulation in functional assessment of cervical and lumbar spinal stenosis in children with achondroplasia. METHOD: We reviewed MN-SEPs, PTN-SEPs, and spinal magnetic resonance imaging (MRI) examinations performed in 58 patients with achondroplasia (25 males, 33 females; age range 21d-16y 10mo; mean age 4y 3mo [SD 4y 1mo]). Patients were subdivided into four age categories: <2 years, between 2 to 4 years, between 4 to 8 years, and ≥8 years. The peak latency of P37 for PTN-SEPs, the peak latencies of N11, N13, P14, and N20, and the N13-N20 interpeak latency (IPL) for MN-SEPs were collected; the diagnostic accuracy measures of these parameters (analysis of receiver operating characteristic [ROC] curves) with respect to the presence of foramen magnum or lumbar spinal stenosis were analysed in each age category. RESULTS: The ROC curve analysis showed that the most sensitive parameter in detecting the presence of foramen magnum stenosis was P37 latency in the first two age categories (<2y and ≥2-4y; sensitivity 0.63, specificity 1.00, and sensitivity 1.00, specificity 0.75 respectively). In the third age category (≥4-8y), the most sensitive parameter in detecting the presence of foramen magnum stenosis was IPLs N13-N20 (sensitivity 0.73, specificity 0.87), whereas in the last age category (≥8y), the most important parameter was N20 latency (sensitivity 0.75, specificity 0.77). INTERPRETATION: In children with achondroplasia, the cortical component of PTN-SEPs is more sensitive than the cortical component and central conduction time of MN-SEPs in detection of cervical spinal cord compression at early ages.

Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and neuroradiological reversibility.

Pyruvate dehydrogenase complex (PDHC) deficiency causes encephalomyopathies, of which there are four major categories: (1) neonatal encephalopathy with lactic acidosis; (2) an early infantile form, which (3) at times resembles Leigh syndrome; and (4) a later-onset form. Long-term clinical and radiological follow-up is still incompletely elucidated. We report a 12-year-old male with intermittent-relapsing PDHC deficiency who presented with three typical acute episodes of metabolic decompensation over 7 years. Neuroimaging showed reversible signal abnormalities in the basal ganglia, inferior olivary nuclei, periaqueductal grey matter, and dentate nuclei, with evidence of lactate on magnetic resonance spectroscopy. Molecular analysis of PDH1A revealed a novel hemizygous c.1045G>A mutation, predicting a p.A349T missense mutation. He was treated with thiamine supplementation and, while on this regimen, he experienced several intercurrent febrile episodes without neurological compromise. This case report stresses the importance of performing neuroimaging during acute clinical episodes because brain lesions in PDHC deficiency may be transient and reversible, and false-negative results may mislead the diagnosis and delay the treatment.

A case of major form familial hyperekplexia: prenatal diagnosis and effective treatment with clonazepam.

Hyperekplexia (OMIM 149400) is an uncommon neurologic disorder characterized by exaggerated response to sensitive stimuli. It may be sporadic or familial. The disease is usually caused by mutations in the inhibitory glycine receptor alpha1-subunit. The authors report a male patient who is affected by the major form of familial hyperekplexia. He is currently 5 years old and is being successfully treated with clonazepam. Prenatal diagnosis was made owing to prior identification of point mutation K276E in his affected mother. Early diagnosis avoided complex and prolonged differential diagnostic procedures and allowed for early and effective intervention on severe neonatal symptoms: hypertonia, episodes of cyanosis, apneic spells, and massive myoclonic jerks. During his first year of life, the patient was treated with cycles of phenobarbital and diazepam and achieved partial clinical response. Subsequent therapy with low-dose clonazepam was highly effective in reducing myoclonic jerks and exaggerated startle reaction, and unlike previously used drugs, it was decisive in reducing hypertonia.

Brown-Vialetto-Van Laere syndrome: clinical and neuroradiological findings of a genetically proven patient.

The Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disorder characterized by progressive pontobulbar palsy, sensorineural deafness and mixed spinal and upper motor neuropathy. Mutations in the C20orf54 gene have been linked to the disease and recently we reported the first Italian case of a BVVLS family with an intriguing C20orf54 genotype. However, the pathomechanisms underlying BVVLS are still unknown. Here we present the particular disease course with partial response to immunosuppressive therapy of our BVVLS patient for whom we hypothesize that dysimmune factors may have played a role in disease physiopathology.

The metabotropic glutamate receptor 1, GRM1: evaluation as a candidate gene for inherited forms of cerebellar ataxia.

The metabotropic glutamate (mGlu) 1 receptor, coded by the GRM1 gene, is involved in synaptic activities, learning and neuroprotection. Eleven different mouse Grm1 mutations, either induced or spontaneously occurring, have been reported, including one from our group. All the mutations result in a complex phenotype with ataxia and intention tremor in mice. Moreover, autoantibodies against mGlu1 receptor have been associated with paraneoplastic cerebellar ataxia in humans. In spite of the large clinical and genetic heterogeneity displayed by the inherited forms of cerebellar ataxia, forms remain with a yet unknown molecular definition. With the evidence coming out from mouse models and from paraneoplastic ataxia, it seems that GRM1 represents a good candidate gene for early-onset ataxia forms, though no GRM1 mutations have thus far been looked for. The aim of this study was to investigate the possible involvement of GRM1 in early-onset or familial forms of ataxia. We searched for gene mutations in a panel of patients with early-onset ataxia as yet molecularly undefined. No causative mutations were found, though we detected synonymous variants in the exons and changes in flanking intronic sequences which are unlikely to alter correct splicing upon bioinformatics prediction. As for other known forms of inherited ataxias, absence of mutations in GRM1 seems to suggest a relatively low frequency in cerebellar ataxias.

Severe neuropathy after diphtheria-tetanus-pertussis vaccination in a child carrying a novel frame-shift mutation in the small heat-shock protein 27 gene.

Mutations in small heat-shock protein 27 and small heat-shock protein 22 genes were found in association with Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy. We searched for mutations in small heat-shock protein 27 gene in an Italian family with peripheral neuropathy and intrafamilial phenotypic variability. A novel heterozygous frame-shift mutation c.476_477delCT was found while point mutations in most genes associated with hereditary neuropathies were ruled out. In the proband, who showed a severe early onset peripheral neuropathy, an independent pathogenetic effect on the peripheral nervous system secondary to the tetanus toxoid injection may be supposed. This is the first truncating nonsense mutation in the small heat-shock protein 27 gene identified so far and the clinical, neurophysiologic, and neuropathological findings are discussed.

Short latency evoked somatosensory potentials after stimulation of the median nerve in children: normative data.

Purpose of the present study was to investigate the early cortical somatosensory evoked potentials after median nerve stimulation and to determine normative data as a function of age. Two hundred forty subjects aged 1 day to 18 years were studied to determine standards of normality during maturation to establish the growth curve. The N9, N13, and N20 components were present in all patients. These components decreased in latency until 4 to 5 years of age because of central nervous system maturation after which latencies increased until adulthood, on the basis of brain and body growth.