Ethosuximide is effective in the treatment of epileptic negative myoclonus in childhood partial epilepsy.

The aim of our study was to evaluate the effectiveness of ethosuximide in the treatment of epileptic negative myoclonus, a motor disorder that can occur in childhood partial epilepsy. We introduced ethosuximide in nine patients with partial epilepsy of varying etiology (idiopathic, cryptogenic, symptomatic) who presented with epileptic negative myoclonus. The drug was added to the patients' preexisting antiepileptic drugs, which were maintained unchanged for the following 6 months. Epileptic negative myoclonus disappeared in all patients 15 to 30 days after ethosuximide was started. Plasma ethosuximide levels ranged from 55 to 89 micrograms/mL. The clinical response was not influenced by the patients' preexisting treatment or by the etiology of the epilepsy. No side effects were observed, and none of the patients presented a recurrence of epileptic negative myoclonus during follow-up. Furthermore, in five patients we observed the disappearance of partial seizures; in the remaining patients seizures were reduced by more than 75%. Electroencephalograms showed a decrement or disappearance of focal paroxysmal abnormalities. Our results suggest that ethosuximide is effective in the treatment of epileptic negative myoclonus and that it should be considered as a first-choice drug in the treatment of this motor disorder.     

Utility of Tc 99m HMPAO SPECT in the early diagnosis of Rasmussen’s syndrome

Neuroradiological examinations are important in the diagnosis of Rasmussen’s syndrome (RS), but they frequently result normal in the early phase of the disease. We performed Tc 99m HMPAO SPECT (single photon emission computed tomography) on an 11-year, 5-month-old, right-handed girl, two months since the first seizure. SPECT showed a reduced uptake of HMPAO in the left temporal region despite normal results with magnetic resonance imaging (MRI). After six months, she developed epilepsia partialis continua, neurological signs appeared, and MRI showed cortical atrophy on the left side. SPECT seems to be a useful, inexpensive and diffuse technology able to give information in the early phases of RS useful in the prevention of serious consequences of the disease within a medical therapeutic program (ganciclovir or intravenous immunoglobulins).

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Sommario è noto che le indagini neuroradiologiche sono importanti nella diagnosi della syndrome di Rasmussen (RS), ma è altrettanto veto che esse risultano spesso normali nelle fasi precoci della malattia. Descriviamo il caso di una paziente di undici anni e cinque mesi, affetta da RS, che è stata sottoposta a Tc 99m HMPAO SPECT due mesi dopo la prima crisi. La SPECT ha mostrato una riduzione della perfusione che interessava il lobo temporale sn, mentre la risonanza magnetica (RMN) risultana normale. Sei mesi più tardi la paziente sviluppava un’epilessia parziale continua e la RMN mostrava una atrofia corticale emisferica sn. Pensiamo che la SPECT sia un esame utile, economico e di largo impiego in grado di fornire ulteriori informazioni, rispetto a quelle già descritte, sulle fasi iniziali della RS. L’individuazione precoce di una RS permette infatti di instaurare una terapia medica (ganciclovir o immunoglobuline) prima della comparsa delle gravi conseguenze della malattia.

     

High rate of PIK3CA mutations but no TP53 mutations in low‐grade adenosquamous carcinoma of the breast

Aims

Low‐grade adenosquamous carcinoma of the breast (LGASC) is a rare variant of metaplastic carcinoma characterised by a favourable outcome and histologically composed of glandular and squamous elements in a spindle cell background typically associated with a lymphocytic stromal reaction. Because of its rarity, the immunophenotypic and genetic profile of LGASC has not been sufficiently characterised. The aim of this study was to gain insights into the molecular and phenotypic characteristics of LGASC.

Methods and results

We reviewed the clinical and morphological features and detailed the immunohistochemical characteristics of a retrospective series of 13 LGASCs. Targeted sequencing of 50 genes was performed in 10 of 13 cases. Identified mutations were further assessed by Sanger sequencing in a validation series of 11 additional cases. All tumours showed a triple‐negative immunophenotype, expressed ‘basal’ keratins, showed variable levels of epidermal growth factor receptor expression, and did not express androgen receptor. Sequencing analysis of the screening set of LGASCs revealed a high rate (seven of 10 cases) of PIK3CA mutations, whereas no TP53 mutations were found. All PIK3CA mutations were missense mutations located either in exon 20 (n = 6) or in exon 9 (n = 1). The global PIK3CA mutation rate, including the validation series, was 52% (11 of 21 cases). No disease recurrences were observed. [Correction added on 11 June 2018, after first online publication: The percentage of mutation rate was corrected to 52%]

Conclusions

Our results indicate that LGASC of the breast is a low‐grade triple‐negative breast cancer that harbours a basal‐like phenotype with no androgen receptor expression, and shows a high rate of PIK3CA mutations but no TP53 mutations.     

Late cerebellar relapse of a juvenile bronchial carcinoid

Although epithelial bronchial neoplasm is a cancer frequently observed in adult patients, it is rarely observed in patients who are children. The most frequent histologic subtype is well differentiated neuroendocrine tumor, or carcinoid. They have a variable biologic behavior, ranging from benign to malignant tumors capable of very late recurrence or metastasis. Liver and lung are frequent sites of carcinoid metastasis, and the central nervous system is exceptionally involved. We report the case of a child with a pulmonary carcinoid initially considered typical, who presented with relapse in the cerebellum and mediastinum 16 years later. After review of the pathology slides, primary and metastatic tumors were reclassified as atypical carcinoid according to the criteria of the 2004 World Health Organization classification of lung tumors. This unusual case emphasizes the value of reviewing pulmonary carcinoids diagnosed before 1998 in order to distinguish typical from atypical lesions and to define follow-up modalities more clearly.     

Antagonism between steady light and phosphodiesterase inhibitors on the kinetics of rod photoresponses.

Treatment of toad rods with phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, caffeine, theophylline, papaverine, and RO 20-1724) modifies the properties of the intracellular voltage responses to dim flashes of light. 3-Isobutyl-1-methylxanthine at 1-20 microM causes an increase in flash sensitivity and a slowing down of the kinetics of the photoresponses. When the drug concentration is greater than 20 microM, rods also show supralinear behavior, whereby doubling the intensity of a dim flash may increase the response by greater than 2-fold. Sensitivity, kinetics, and supralinear behavior can be restored to normal by steady background illumination while still in the presence of 3-isobutyl-1-methylxanthine. However, the intensity of the steady light needed to restore the sensitivity to control levels is not sufficient to accelerate the kinetics back to control values. The antagonism between the effects of 3-isobutyl-1-methylxanthine and the effects of background illumination is explained by assuming that: (i) the length of time to peak voltage responses to dim flashes of light is inversely proportional to the rate of a chemical reaction; (ii) the rate of this reaction is controlled by an enzyme that is inhibited competitively by 3-isobutyl-1-methylxanthine with a Ki of 3 x 10(-6) M; and (iii) the concentration of a cofactor of this reaction increases proportionally with the intensity of the background illumination.     

Characteristics of a large population of patients with refractory epilepsy attending tertiary referral centers in Italy

The characteristics of 1,124 consecutive adults and children with refractory epilepsy attending 11 tertiary referral centers in Italy were investigated at enrollment into a prospective observational study. Among 933 adults (age 16–86 years), the most common syndromes were symptomatic (43.7%) and cryptogenic (39.0%) focal epilepsies, followed by idiopathic (8.1%) and cryptogenic/symptomatic generalized (6.2%) epilepsies. The most common syndrome among 191 children was symptomatic focal epilepsy (35.1%), followed by cryptogenic focal (18.8%), cryptogenic/symptomatic generalized (18.3%), undetermined whether focal or generalized (16.8%), and idiopathic generalized (7.3%). Primarily and secondarily generalized tonic–clonic seizures were reported in 27.8% of adults and 16.8% of children. The most commonly reported etiologies were mesial temporal sclerosis (8.0%) and disorders of cortical development (6.2%) in adults, and disorders of cortical development (14.7%) and nonprogressive encephalopathies (6.8%) in children. More than three‐fourths of subjects in both age groups were on antiepileptic drug (AED) polytherapy.     

The spectrum of benign myoclonus of early infancy: Clinical and neurophysiologic features in 102 patients

Purpose:   To redefine benign myoclonus of early infancy (BMEI) through analysis of clinical and neurophysiologic features in 102 patients with the aim to widen the spectrum of the syndrome, including a number of different clinical expressions of transient nonepileptic paroxysmal movements occurring in normal infants.
Methods:   We recruited patients from one center in Argentina and two in Italy, including infants with normal neurologic and psychomotor development presenting with brief paroxysmal abnormal movements. Children with motor phenomena occurring only during sleep were excluded. Patients with abnormal interictal or ictal electroencephalography (EEG) findings were also excluded. The follow-up ranged from 2–40 years.
Results:   One hundred and two infants (60 male) met the inclusion criteria. Age at onset ranged from 1–12 months, with a median age of 6.2 months. The following nonepileptic paroxysmal motor phenomena were recognized: (1) myoclonus, (2) spasms and brief tonic contractions, (3) shuddering, (4) atonia or negative myoclonus, (5) more than one type of motor phenomenon. In the majority of cases the episodes occurred only while awake and repeated several times a day. In 45 (44.1%) of the 102 cases contractions appeared in clusters.
Conclusions:   Based on the analysis of clinical and EMG features in this large series of infants, we postulate that the spectrum of the syndrome is wider than initially suspected, and that the different transient motor manifestations and their correlation with different EMG patterns will allow recognition of this definitely benign condition comprising a variety of episodic motor phenomena in normal babies.