Distal myopathy with upper limb predominance caused by filamin C haploinsufficiency.

OBJECTIVE: In this study, we investigated the detailed clinical findings and underlying genetic defect in 3 presumably related Bulgarian families displaying dominantly transmitted adult onset distal myopathy with upper limb predominance. METHODS: We performed neurologic, electrophysiologic, radiologic, and histopathologic analyses of 13 patients and 13 at-risk but asymptomatic individuals from 3 generations. Genome-wide parametric linkage analysis was followed by bidirectional sequencing of the filamin C (FLNC) gene. We characterized the identified nonsense mutation at cDNA and protein level. RESULTS: Based on clinical findings, no known myopathy subtype was implicated in our distal myopathy patients. Light microscopic analysis of affected muscle tissue showed no specific hallmarks; however, the electron microscopy revealed changes compatible with myofibrillar myopathy. Linkage studies delineated a 9.76 Mb region on chromosome 7q22.1-q35 containing filamin C (FLNC), a gene previously associated with myofibrillar myopathy. Mutation analysis revealed a novel c.5160delC frameshift deletion in all patients of the 3 families. The mutation results in a premature stop codon (p.Phe1720LeufsX63) that triggers nonsense-mediated mRNA decay. FLNC transcript levels were reduced in muscle and lymphoblast cells from affected subjects and partial loss of FLNC in muscle tissue was confirmed by protein analysis. CONCLUSIONS: The FLNC mutation that we identified is distinct in terms of the associated phenotype, muscle morphology, and underlying molecular mechanism, thus extending the currently recognized clinical and genetic spectrum of filaminopathies. We conclude that filamin C is a dosage-sensitive gene and that FLNC haploinsufficiency can cause a specific type of myopathy in humans.

Long-term survival with primary glioblastoma multiforme: a clinical study in bulgarian patients.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with an extremely poor prognosis in spite of multimodal treatment approaches. The estimated median survival in cases with GBM is about 12-16 months. Those patients who survive =3 years after the initial diagnosis are defined as long-term survivors. In this study, we retrospectively analyze 50 consecutive cases of Bulgarian patients with newly diagnosed GBM surgically treated at our institution for a period of 1 year. Four of them survived for more than 36 months after the initial intervention. The histological re-examination revealed features typical of primary GBM in 3 of these cases, which are described in detail in the present paper. A brief review of the relevant literature is also given.

Cerebellar gangliocytoma presenting with hemifacial spasms: clinical report, literature review and possible mechanisms.

Cerebellar lesions have classically been considered not to cause epilepsy. However, previous reports have attributed seizures, beginning as hemifacial spasms to lesions of the cerebellar peduncles. We report an example of paroxysmal facial contractions associated with a cerebellar gangliocytoma. The seizures began on the first day of life and consisted of paroxysmal contractions involving the left orbicularis oculi, often the left forehead and lower facial muscles, sometimes accompanied by nystagmoid eye movements to the right and by head deviation to the left. Video-EEG monitoring showed only artifacts from muscle contractions. Magnetic resonance imaging showed a mass arising from the left superior cerebellar peduncle and partially occupying the fourth ventricle. The lesion was removed subtotally and partial seizure control was achieved. The neuropathological findings were consistent with a gangliocytoma. The literature in the association of cerebellar lesions with hemifacial spasms is reviewed and its possible mechanisms discussed.

Acquired benign esophago-airway fistulas.

MATERIALS AND METHODS: Over a period of 25 years, 35 patients with acquired benign esophago-airway fistulas were treated. Only two of them were female. The etiology of the communications was corrosive burns, penetrating wounds, postoperative and endoscopic lesions, esophageal diverticula, prolonged ventilatory assistance, pleural empyema and foreign bodies. Radical operative treatment was performed in 31 cases. In four of these the procedure was palliative, because of poor general condition and lung complications. The operative approach was chosen after precise endoscopic and contrast X-ray examinations. A cervical approach with partial median sternotomy to the third intercostal space was performed in 19 patients. In the rest of the patients a thoracotomy was performed. Simple excision of the fistula, longitudinal suture of the trachea and horizontal suture of the esophagus was the method of choice in nine patients. A flap from the left sternocleidomastoid was additionally interposed in front of the esophagus in 12 patients. In six cases circular resection, reconstruction of the trachea and plastic suture of the esophagus were performed. Esophagectomy with ensuing colon substitution was necessary in four patients. RESULTS: Excellent or good results were obtained in 29 of the 31 patients operated on. We had two deaths in the early postoperative period (6.8%) due to lung complications in patients with chemical burns of the esophagus. The operated patients were followed up for period ranging from 3 to 20 years. CONCLUSION: Acquired esophago-respiratory fistulas require emergency surgical treatment. The proper choice of operative approach is largely dependent on the precise diagnosis. Preoperative intensive care and metabolic balance are important factors in this report. Radical operative treatment depends on the basic disease, local inflammation and lung complications.

Neuroophthalmological symptoms in children treated for internal hydrocephalus.

The object of the study are 126 children with internal hydrocephalus treated within the period 1978-1990. The children were preoperatively divided into six groups according to the etiology of the hydrocephalus. Disorders of the visual functions accompanying elevated intracranial pressure (setting sun 51, syndrome of the aqueduct of Sylvius 14, paresis of craniocerebral nerves 9, nystagmus 8, optic atrophy 4) were established preoperatively in 48.4% of the children. 44 of the children were revised because of malfunction of the shunt with the following neuroophthalmological symptoms: setting sun 6, paresis of craniocerebral nerves 9, syndrome of the Sylvius aqueduct 6, papilledema 6, optic atrophy 9 and nystagmus 5. The fact that a great many changes in the visual functions sometimes precede the manifestations of the changes in CT image determines their significance for early diagnosis and treatment.

Eosinophilia in the cerebrospinal fluid of children with shunts implanted for the treatment of internal hydrocephalus.

Cerebrospinal fluid (CSF) eosinophilia was observed in 26 of 404 children after the implantation of shunts for the treatment of internal hydrocephalus. High levels of 65% and 78% were recorded in two cases, which are reported in detail. In the remaining 24 cases, CSF eosinophilia ranging between 1% and 3% was found. None of the cases with CSF eosinophilia had blood eosinophilia. The cases indicate that a reaction to the material used for the shunt should be considered along with possible parasitic infestations in patients with such findings.