Elvio Della Giustina

Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.

Mowat–Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70–75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti‐epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1–108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow‐up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near‐to‐continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age‐dependent EEG changes, can be recognized in most patients with MWS.

Acute and chronic corticosteroid treatment of ten patients with paralytic form of Sydenham's chorea

AIMS To determine efficacy and safety of corticosteroid treatment in patients with severe Sydenhams chorea paralytic form. METHODS This is a 4 years observational study on ten patient with severe paralytic form of Sydenhams chorea unresponsive to neuroleptics and antiepileptics agents, treated with intravenous methylprednisolone followed by oral deflazacort therapy. Chorea paralytica patients were bedridden, unable to take independent steps, showed severe generalized hypotonia and were hospitalized for 3-4 weeks. Additional clinical evaluations were undertaken at 1, 3 and 6 months and 1, 2 and 4 years from onset of chorea. Severity chorea at the onset and during follow up was rated according to Universidade Federal de Minas Gerais (UFMG) Sydenhams Chorea Rating Scale (USCRS). In all children video-recording was performing at onset and during clinical follow-up. RESULTS We reported a significant improvement in swallowing and chewing with partial recovery of language 2-3 days after starting intravenous methylprednisolone treatment and complete disappearance of movement disorders after 3-4 weeks of treatment. All our patients were followed for 4 years from onset and none experienced relapse of chorea, other movement disorders or psychiatric disturbances. The treatment with deflazacort was well-tolerated in all children with no significant side effects reported. CONCLUSION Our data showed that high dose of methylprednisolone intravenously followed by deflazacort therapy may be effective and well-tolerated in children with severe paralytic form of Sydenhams chorea.

Hereditary spastic paraplegia and axonal motor neuropathy caused by a novel SPG3A de novo mutation

Mutations in the SPG3A gene (atlastin protein) cause approximately 10% of autosomal-dominant hereditary spastic paraplegia. Most patients with an SPG3A mutation present with a pure phenotype and early-onset disease, although complicated forms with peripheral neuropathy are also reported. We report a new heterozygous S398F mutation in exon 12 of the SPG3A gene causing a very early-onset spastic paraplegia in association with motor axonal neuropathy in a 4-year-old girl resembling diplegic cerebral palsy.

Coexistent Central and Peripheral Nervous System Involvement in a Charcot-Marie-Tooth Syndrome X-linked Patient

A 14-year-old boy with an episode of acute weakness resembling acute demyelinating encephalomyelitis and polyradiculoneuritis after a febrile illness is described. Molecular analysis showed a mutation at codon 164 of the connexin 32 gene. Neuroradiological and neurophysiological follow-up is reported during acute and chronic phases of disease, suggesting that during metabolic stress connexin 32 mutations lead to a loss of normal cellular communication and reversible cell dysfunction in oligodendrocytes and in Schwann cells. These data confirm that altered gating properties of connexin 32 could give rise to acute, transient central and peripheral nervous system symptoms in situations of metabolic stress.

Stress fracture of the peroneal bone secondary to a complex tic

Complex tics have been widely reported in literature, especially in children with Tourette syndrome. We describe the case of a fracture line of both peroneal bones in a 13-year-old child with Tourette syndrome and obsessive-compulsive disorder. He was admitted to our hospital because of pain in his legs. Radiography showed fractures of both peroneal bones, more marked on the left side. The clinical history was strongly suggestive of obsessive-compulsive disorder and Tourette syndrome with associated simple and complex motor tics. Radiographic follow-up showed spontaneous resolution of the fractures.

Partial epilepsy complicated by convulsive and nonconvulsive episodes of status epilepticus in a patient with ring chromosome 14 syndrome

Epilepsy is the most common and serious neurological symptom in ring chromosome 14 syndrome, also characterised by mild dysmorphisms, acquired microcephaly, cognitive impairment, hypotonia and ocular abnormalities. Typically, early-onset, polymorphous and drug-resistant seizures are reported. Status epilepticus has not been previously reported. We describe a nine-year-old Caucasian boy with ring 14 syndrome who presented a severe early-onset and drug-resistant focal epilepsy with secondary generalised seizures and repetitive episodes of convulsive and non-convulsive status epilepticus. The electro-clinical evaluation of prolonged seizures and their long-term consequences is important for the practical management of these patients and for a better comprehension of the syndrome.

Early onset methylmalonic aciduria and homocystinuria cblC type with demyelinating neuropathy.

Methylmalonic aciduria and homocystinuria, cblC type, is the most common inborn error of vitamin B(12) (cobalamin) metabolism. The recent cloning of the disease gene, MMACHC, has permitted genotype-phenotype correlation. In a 1-year-old girl, compound heterozygous c.271dupA and c.616C>T mutations in MMACHC were identified as causing an early onset methylmalonic aciduria and homocystinuria, cblC type, which was complicated by sensorimotor peripheral demyelinating neuropathy.

Epilepsy in ring 14 syndrome: a clinical and EEG study of 22 patients

To characterize epileptic phenotype, electroencephalography (EEG) features, and epileptic evolution in patients with ring 14 r(14) syndrome.

Transient Basal Ganglia and Thalamic Involvement Following Mycoplasma pneumoniae Infection Associated With Antiganglioside Antibodies

A case of acute and reversible bilateral basal ganglia with thalami involvement associated with serological evidence of Mycoplasma pneumoniae infection is reported. Increased titers of immunoglobulin M antibodies against GM1 ganglioside components were found during an acute phase of neurological illness. Brain magnetic resonance imaging (MRI) showed bilateral involvement of the basal ganglia and thalamus, which disappeared 1 month later. The child recovered fully after corticosteroid and immunoglobulin therapy, and antiganglioside antibodies returned to within the normal range. The authors speculate on the diagnostic hypothesis regarding selective basal ganglia and thalamic involvement and the relationship with anti-GM1 ganglioside immunoglobulin M antibodies.

Isolated Vitamin E Deficiency Mimicking Distal Hereditary Motor Neuropathy in a 13-Year-Old Boy

We report an atypical neurophysiologic pattern of isolated vitamin E deficiency in a 13-year-old boy. Electroneurography— electromyography, somatosensory evoked potentials, serum vitamin E concentration and genetic analysis of the α-tocopherol transfer protein gene were performed. Nerve conduction study failed to show peripheral neuropathy whereas needle electromyography of distal muscles demonstrated chronic neurogenic motor unit potentials. Both clinical and neurophysiologic data fulfilled the criteria of distal hereditary motor neuropathy. Later on, somatosensory-evoked potential displayed absence of spinal and central response. The serum vitamin E level was low, and the patient was found to be homozygous for a 513insTT mutation in exon 3 of the α-tocopherol transfer protein gene. To our knowledge this is the first case of isolated deficiency of vitamin E that presents the classic neurophysiologic and clinical features of distal hereditary motor neuropathy.