Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark of cerebellar and optic pathway tumours.

BACKGROUND: Juvenile pilocytic astrocytomas (JPA), a subgroup of low-grade astrocytomas (LGA), are common, heterogeneous and poorly understood subset of brain tumours in children. Chromosomal 7q34 duplication leading to fusion genes formed between KIAA1549 and BRAF and subsequent constitutive activation of BRAF was recently identified in a proportion of LGA, and may be involved in their pathogenesis. Our aim was to investigate additional chromosomal unbalances in LGA and whether incidence of 7q34 duplication is associated with tumour type or location. METHODS AND RESULTS: Using Illumina-Human-Hap300-Duo and 610-Quad high-resolution-SNP-based arrays and quantitative PCR on genes of interest, we investigated 84 paediatric LGA. We demonstrate that 7q34 duplication is specific to sporadic JPA (35 of 53 - 66%) and does not occur in other LGA subtypes (0 of 27) or NF1-associated-JPA (0 of 4). We also establish that it is site specific as it occurs in the majority of cerebellar JPA (24 of 30 - 80%) followed by brainstem, hypothalamic/optic pathway JPA (10 of 16 - 62.5%) and is rare in hemispheric JPA (1 of 7 - 14%). The MAP-kinase pathway, assessed through ERK phosphorylation, was active in all tumours regardless of 7q34 duplication. Gain of function studies performed on hTERT-immortalised astrocytes show that overexpression of wild-type BRAF does not increase cell proliferation or baseline MAPK signalling even if it sensitises cells to EGFR stimulation. CONCLUSIONS AND INTERPRETATION: Our results suggest that variants of JPA might arise from a unique site-restricted progenitor cell where 7q34 duplication, a hallmark of this tumour-type in association to MAPK-kinase pathway activation, potentially plays a site-specific role in their pathogenesis. Importantly, gain of function abnormalities in components of MAP-Kinase signalling are potentially present in all JPA making this tumour amenable to therapeutic targeting of this pathway.

[Pain and amyotrophy in upper members in a cirrhotic patient with Pott's disease]. / Dolor y amiotrofia en miembros superiores en una paciente cirrótica afecta del mal de Pott.

We report the case of a 56 year old cirrhotic woman who presented during the course of a tuberculous spondylodiscitis affecting T9-T10, a clinical picture consistent with neuralgic amyotrophy affecting the right shoulder first, and later also the left one (Parsonage-Turner syndrome). This is an uncommonly diagnosed entity of unknown etiology and pathogenesis. Magnetic resonance images (MRI) include high signal intensity in supra and infraspinatus muscles and other muscles of the shoulder girdle, compatible with muscle oedema associated with denervation. These features, combined with the ability of MRI to exclude local problems as tendinitis stresses the importance of this technique in the diagnostic evaluation of patients with neuralgic amyotrophy.

Radionuclide shuntogram: adjunct to manage hydrocephalic patients.

UNLABELLED: We reviewed our experience with shuntograms to establish technical criteria that would optimize the reliability of this test in managing patients with shunt malfunction. METHODS: Fifty-six shuntograms were performed in 47 children presenting with symptoms of shunt malfunction not elucidated by conventional radiological examination. Shuntograms were performed by injecting 0.5 ml 99mTc-DTPA in the reservoir of the shunt. RESULTS: There were 22 shuntograms in which ventricular reflux occurred and the entire shunt system was visualized. At surgery, three patients in this group presented partial obstruction of the ventricular and/or peritoneal catheter. A second group of patients had 15 shuntograms that showed normal proximal reflux but abnormal distal drainage. Ten patients in this group presented distal obstruction or fracture, valve dysfunction or peritoneal adhesions at surgery. A third group of patients with 19 shuntograms exhibited no proximal reflux. At surgery, twelve had an obstructed ventricular catheter and the last case showed overdrainage. Symptoms of nonsurgical patients abated spontaneously. CONCLUSION: The shuntogram is a useful procedure in the management of patients presenting with shunt-related problems. For consideration as a normal result, a shuntogram must exhibit ventricular reflux, the shunt system must be entirely visualized and the isotope must diffuse uniformly in the peritoneal cavity. Whereas rapid radionuclide clearance is a useful parameter in eliminating a distal obstruction. It is a misleading sign for proximal blockage. Absence of ventricular reflux is highly suggestive of proximal reflux. Implicit to this conclusion is the fact that the presence of a reservoir proximal to the valve greatly facilitates the performance and interpretation of a shuntogram.

Cerebral arterial ectasia and tuberous sclerosis: case report.

OBJECTIVE AND IMPORTANCE: Tuberous sclerosis is associated with a wide variety of central nervous system abnormalities. Cerebrovascular anomalies are extremely rare, but a case of cerebral arterial ectasia and giant fusiform aneurysm formation in a young child is reported. CLINICAL PRESENTATION: A 5-month-old male patient with tuberous sclerosis presented with seizures, a subependymal tumor, and intraventricular hemorrhage. Cerebral angiography demonstrated a large fusiform aneurysm of the left cavernous internal carotid artery as well as arterial ectasia of the proximal left anterior cerebral and middle cerebral arteries. The patient developed hydrocephalus and died of infectious complications after repeated shunt procedures. CONCLUSION: Tuberous sclerosis is commonly associated with central nervous system lesions. Although rare, cerebrovascular anomalies and aneurysms should be considered in the differential diagnosis of mass lesions to avoid an ill-advised biopsy of a vascular lesion, which could have disastrous consequences.

Negative-pressure hydrocephalus.

Two cases of children with closed myelodysplasia, Arnold-Chiari malformation, and shunted hydrocephalus who underwent spinal arachnoid cystopleural shunting are presented. Postoperatively, both patients developed craniovertebral symptomatology accompanied by radiologically documented ventricular dilation in spite of negative intracranial pressure and functional ventriculoperitoneal (VP) shunts. Both patients recovered after the cystopleural shunts were revised to increase the resistance to flow within the system. The authors believe that some communication between the arachnoid cyst and the subarachnoid space existed in both cases and that the negative pleural pressure was transmitted preferentially to the spinal and cerebral convexity subarachnoid spaces with relative sparing of the ventricular system. A transmantle pressure gradient was thereby established, leading to ventricular dilation. The authors further suggest that a craniospinal gradient was possibly established as well, leading to craniovertebral symptomatology in the patients. Return of flow in the VP shunts was obtained by correcting this iatrogenic transmantle pressure gradient.

Comparison of syringopleural and syringosubarachnoid shunting in the treatment of syringomyelia in children.

Case records from the Montreal Children's Hospital containing the diagnosis of shunted syringomyelia were retrospectively reviewed. From 1984 to 1994, 31 patients had their syrinx treated by either syringopleural (19 cases, Group A) or syringosubarachnoid (13 cases, Group B) shunting. One patient was included in both groups. Associated diagnoses included: in Group A, two cases of Chiari I and 14 of Chiari II malformations, 14 cases of shunted hydrocephalus, 13 cases of spina bifida aperta, and three cases of spina bifida occulta; Group B, four cases of Chiari I and two of Chiari II malformations, four cases of shunted hydrocephalus, two cases of spina bifida aperta, and five cases of spina bifida occulta. Eight Group A and six Group B patients had undergone prior posterior fossa decompression. Motor deficits predominated in both groups and arachnoiditis was a uniform operative finding. Neurological follow-up examinations showed 11 Group A patients improved and eight stabilized, whereas on magnetic resonance imaging, 12 cavities appeared to have collapsed, five were markedly reduced, and one had increased. One patient underwent reoperation for pleural effusions and one for shunt displacement. In Group B, one patient improved, eight stabilized, three worsened neurologically, and one was lost to follow-up review. Radiologically, one cavity appeared to have collapsed, six were significantly reduced, two were unchanged, and three had enlarged. The authors conclude that syringopleural shunting is a valuable option for controlling syringomyelia in patients without Chiari malformation or in patients who have previously undergone a craniovertebral decompression or are otherwise asymptomatic from their Chiari malformation.

Stereotactic transtentorial hiatus ventriculoperitoneal shunting for the sequestered fourth ventricle. Technical note.

The authors describe a technique of stereotactic transtentorial hiatus ventriculoperitoneal shunting for the treatment of the sequestered fourth ventricle, used successfully in the care of four patients. They recommend it as a safe, effective treatment of patients suffering from an isolated fourth ventricle.

Impact of urodynamic studies on the surgical management of spinal cord tethering.

To determine the usefulness of urodynamic studies in the management of children with a suspected tethered spinal cord, the authors retrospectively reviewed case records of 25 patients evaluated both pre- and postoperatively using this diagnostic adjunct. All patients were also evaluated with magnetic resonance imaging or computerized tomography myelography. Seven patients who presented initially with orthopedic deformity, skin stigmata, and neurological problems underwent primary cord untethering (Group 1). All seven patients were urologically asymptomatic; all but one had normal findings on urodynamic study. Eighteen patients with prior myelomeningocele closure underwent secondary untethering (Group 2). They presented with urological (11 cases), neurological (three cases), or both urological and neurological (four cases) deterioration. All patients underwent surgery via a microsurgical technique. At a mean follow-up time of 2 years, the only Group 1 patient with preoperative abnormal urodynamic findings normalized following untethering, whereas another asymptomatic patient showed worsened results on his postoperative study. In Group 2, all seven patients with preoperative neurological deterioration improved. Ten of the 15 patients who had isolated or associated preoperative clinical urological deterioration improved or stabilized, whereas five displayed continued deterioration in their bladder function. With respect to urodynamic studies, there was a significant increase in total and pressure-specific bladder capacities following untethering. We conclude that urodynamic studies are useful both diagnostically and in follow-up examinations of patients with tethered cord, that disturbances identified by these studies often precede clinical manifestations of deterioration, and that spinal cord untethering favorably influences the urological status in most patients.

Intractable epilepsy after a functional hemispherectomy: important lessons from an unusual case. Case report.

Residual seizures after functional hemispherectomy occur in approximately 20% of patients with catastrophic epilepsy. These episodes are traditionally attributed to incomplete disconnection, persistent epileptogenic activity in the ipsilateral insular cortex, or bilateral independent epileptogenic activity. The authors report on the case of an 8-year-old boy with an intractable seizure disorder who had classic frontal adversive seizures related to extensive unilateral left hemispheric cortical dysplasia. The initial intervention consisted of extensive removal of the epileptic frontal and precentral dysplastic tissue and multiple subpial transections of the dysplastic motor strip, guided by intraoperative electrocorticography, Subsequently, functional hemispherectomy including insular cortex resection was performed for persistent attacks. After a seizure-free period of 6 months, a new pattern ensued, consisting of an aura of fear, dystonic posturing of the right arm, and unusual postictal hyperphagia coupled with an interictal diencephalic-like syndrome. Electroencephalography and ictal/interictal single-photon emission computerized tomography were used to localize the residual epileptic discharges to deep ipsilateral structures. Results of magnetic resonance imaging indicated a complete disconnection except for a strip of residual frontobasal tissue. Therefore, a volumetric resection of the epileptogenic frontal basal tissue up to the anterior commissure was completed. The child has remained free of seizures during 21 months of follow-up review. Standard hemispherectomy methods provide extensive disconnection, despite the presence of residual frontal basal cortex. However, rarely, and especially if it is dysplastic, this tissue can represent a focus for refractory seizures. This is an important consideration in determining the source of ongoing seizures posthemispherectomy in patients with extensive cortical dysplasia. It remains important to assess them fully before considering their disease refractory to surgical treatment.

Ganglioglioma presenting as a vascular lesion in a 10-year-old boy. Case report.

The authors present the case of a 10-year-old boy admitted for evaluation of a generalized seizure and a history of headaches. Computerized tomography (CT) and gadolinium-enhanced magnetic resonance (MR) imaging demonstrated a large nonhomogeneous contrast-enhancing mass of the left frontal lobe, with a large cystic component. Cerebral angiography revealed the lesion to be highly vascular and fed entirely by the internal carotid artery system. The patient underwent craniotomy and the lesion was completely removed. Neuropathological study revealed that the tumor was a ganglioglioma. On review of the literature, it was found that gangliogliomas often present in the second and third decade, are known to have cystic components, and are contrast-enhancing on CT and MR imaging; however, they are classically known to be avascular on angiography. This case of a markedly vascular ganglioglioma emphasizes that these tumors should be included in the differential diagnosis of vascular supratentorial lesions.

Supratentorial ectopic ependymoma.

BACKGROUND: Ependymomas usually arise from the ventricular surface. METHODS: We report an 11-year-old female who presented with a supratentorial ectopic ependymoma. RESULTS: The patient presented with a two-month-history of progressive headache, nausea and vomiting. Examination revealed papilledema, horizontal nystagmus, diplopia on upward gaze, and right pronator drift. CT scan showed an enhancing left precentral subcortical lesion measuring 3 cm in diameter with associated edema and mass effect. Its medial border was located 3 cm from the ependymal surface of the ventricle. A firm tumour was dissected from the centrum semiovale white matter, and removed in toto as confirmed on MRI. Pathological examination revealed histological, immuno-histochemical and electron microscopic features consistent with an ependymoma. Spine MRI and bone marrow aspirate, as well as lumbar puncture of cytology failed to show any dissemination. CONCLUSION: From the literature review, this represents an exceptional ependymoma located at the distance from the ventricular system or cisterns. Different pathogenic alternatives are discussed.

Intraventricular central neurocytoma.

A case of central neurocytoma treated surgically is described. The authors review the literature. Emphasis is placed on radiological and pathological features not previously described. In particular, the intra-operative ultrasound appearance is described. The role of adjunctive radiotherapy is also discussed.

Newborn apnea caused by a neurofibroma at the craniocervical junction.

The authors report, for the first time, the finding by magnetic resonance imaging of a neurofibroma at the craniocervical junction with upper cervical cord and lower brainstem compression causing complete apnea from birth. Subsequent subtotal resection of the neurofibroma resulted in the successful extubation of a previously ventilator-dependent patient. After a two month period of breathing spontaneously, the newborn developed an upper respiratory tract infection and was reintubated. The patient, unable to be weaned off of the respirator, was extubated and expired shortly thereafter, at the age of five months. The authors suggest that in newborns with unexplained apnea, MRI of the cranio-cervical junction is indicated. Certain patients may be discovered who have less compromised cervico-medullary function and are afflicted by less aggressive forms of neurofibromatosis type 1. These patients may benefit permanently from a surgical decompression.

Neonatal dural sinus thrombosis.

Dural sinus thrombosis in the newborn period has been infrequently documented and its clinical presentation remains obscure. Seventeen patients, all of whom were born at term with dural sinus thrombosis diagnosed in the neonatal period, were retrospectively identified and reviewed. Diagnosis was determined by unenhanced computed tomography which demonstrated a dense sagittal sinus with concomitant small ventricles. Two patients had ancillary studies (i.e., cerebral angiography and nuclear flow scan) which confirmed the diagnosis. Only 4 patients had evidence of perinatal asphyxia. Three patients were identified as having associated conditions known to predispose them to dural sinus thrombosis. None of the patients tested had an identifiable hypercoagulable state. Neonatal seizures were the initial presentation in 15 patients. Seizure onset predominantly occurred during the first week of life. Subsequent examinations were available in all 17 patients and ranged up to 6 years. Only 3 patients had seizures beyond the neonatal period. In 11 of 12 infants with no history of perinatal asphyxia, neurodevelopmental outcomes were normal. Two of 4 infants with perinatal asphyxia had neurologic sequelae. Dural sinus thrombosis represents an important and under-recognized cause of neonatal seizures in term infants. In the absence of perinatal asphyxia, normal neuro-developmental outcome is likely and the risk of seizure recurrence is low.

"Pseudo-BECRS": intracranial focal lesions suggestive of a primary partial epilepsy syndrome.

Benign epilepsy of childhood with rolandic spikes (BECRS) is an electroclinical entity that is the most common primary partial epilepsy syndrome of childhood. Typically presenting between the ages of 3 and 13 years, it is characterized by a well-recognized seizure pattern arising in a normal child with EEG findings restricted to rolandic/centrotemporal regions. Seizure control is usually easily achieved and prognosis is believed to be uniformly good. Some authors have suggested that individuals fitting the electroclinical parameters of this entity need not undergo neuroimaging due to the benign evolution of this disorder. Five patients presenting over a 13-year period with peribuccal seizures, normal neurologic examinations, and EEG data initially suggestive of BECRS found to have focal lesions on neuroimaging are summarized. Independent bilateral centrotemporal epileptiform abnormalities were seen in 3 patients. Imaging studies (CT, MRI, or both) documented a mass lesion in all in variable locations. Histologic examination documented a low-grade astrocytoma in 3 patients and a cavernous angioma in another. The fifth patient refused treatment or biopsy. Careful retrospective review of the clinical features of these patients reveals variable atypical features in each. Therefore, despite an electroclinical phenotype initially suggestive of the BECRS presentation, the presence of atypical clinical features raises the possibility of an underlying structural lesion and thus a negative neuroimaging study may in some patients be essential to the definitive accurate diagnosis of BECRS.

Encephaloduroarterio-synangiosis in a child with sickle cell anemia and moyamoya disease.

We report a black girl with sickle cell anemia. On prophylactic exchange transfusion protocol, she experienced cerebrovascular accidents at 3 and 3.5 years of age, both associated with transient right hemiparesis. At 7.5 years of age, she presented with a partial motor seizure and a left hemiparesis. A cerebral angiogram demonstrated stenosis at the origins of both middle and anterior cerebral arteries bilaterally with extensive basal collateralization. She underwent uncomplicated bilateral encephaloduroarteriosynangiosis (EDAS) procedures using both superficial temporal arteries. At age 9 years, the patient presented with a severe headache and tunnel vision secondary to a stenosis of both posterior cerebral arteries. She underwent bilateral EDAS procedures using both occipital arteries. No complication was encountered. Postoperative cerebral angiogram demonstrated impressive neovascularity at the sites of all four EDAS procedures. Different treatment options of moyamoya disease are discussed.

Cauda equina histiocytosis X.

A young child was admitted with a cauda equina syndrome believed to be progressive, but unrelated to a congenital anomaly. Magnetic resonance imaging studies revealed the presence of an intradural tumor in the cauda equina. A yellow pasty tumor with nerve root infiltration was identified at surgery. Histologic features were pathognomonic for histiocytosis X. The patient's management and review of the literature are discussed.

Encephaloduroarteriosynangiosis (EDAS) for the treatment of childhood moyamoya disease.

Moyamoya disease is defined by the angiographic demonstration of stenosis or occlusion of the vessels of the anterior circulation at the base of the brain and the concomitant development of collateral blood supply. Untreated, the disease is often clinically progressive, resulting in significant neurologic sequelae. Encephaloduroarteriosynangiosis (EDAS), which involves the transposition of a segment of a scalp artery onto the surface of the brain, is a surgical treatment aimed at improving collateral blood flow. Six children underwent 8 EDAS procedures and were followed from 6 months to 9 years after surgery. No patient experienced further deterioration in neurologic status. Postoperative angiography demonstrated cerebral revascularization from the donor scalp artery on 3 of the 6 EDASs that were studied. The 2 patients who did not revascularize after EDAS demonstrated angiographic regression of their disease. The data suggest that EDAS is a safe procedure for the treatment of childhood moyamoya disease. Given the potential severity of the sequelae, early operative intervention is recommended in all children with this disease.

[Hypothalamic hamartoma: detailed presentation of a case]. / Hamartome hypothalamique: présentation détaillée d'un cas.

We describe a seven year old child with a hypothalamic hamartoma. Classical symptoms of hypothalamic hamartoma include gelastic epileptic laughter, precocious puberty, aggressiveness, and progressively worsening epilepsy. After a normal first few years of life, this case presents all these symptoms except the precocious puberty. He has a markedly morbid personality disorder: he assaults strangers and relatives, bites people, spits in their faces unpredictably, is coprolalic and coprophagic, has gelastic laughter, puts pencils, erasers, and other non-comestible objects in his mouth, chews and ingests them, has tics (plays noisily with his saliva, empty chewing, compulsive spitting) and is self-injurious. None of the medications attempted to date have been of any help. Medical prognosis is somber, and this case is difficult to institutionalize, the more "congenial" institutions being insufficiently equipped to protect him and the beneficiaries and staff from his aggressive behavior. MRI showed the typical profile of hypothalamic hamartoma, and the diagnosis was confirmed with partial resection. This case illustrates that a tiny lesion, the size of a small cherry, can have extremely morbid psychological consequences. Detailed neuropsychological evaluation, certain unusual electroencephalographic traits and neurosurgical issues are discussed.

Effectiveness of a head injury program for children: a preliminary investigation.

OBJECTIVE: The purpose of this study was to investigate whether a more coordinated, comprehensive head injury rehabilitation program provided at a children's trauma center yielded better outcomes than a less coordinated, less comprehensive program. DESIGN: Using a quasi-experimental design, 64 children with head injury admitted to the center and who received rehabilitation services in either 1995 or 1993 were evaluated by using the Functional Independence Measure for children (WeeFIM)/The Functional Independence Measure (FIM) (e.g., primary outcome measure). Secondary outcomes included "psychosocial adjustment," "return to regular school," and "current problems related to the head injury." RESULTS: No statistically significant differences were found between the groups with respect to mean WeeFIM/FIM scores after controlling for age and injury severity. The 1993 group had poorer scores on the withdrawal subscale of the psychosocial measure (P = 0.02), yet a smaller proportion of these children were enrolled in a special education class (P = 0.02). CONCLUSIONS: This study serves as a model for a larger, definitive study of the effectiveness of rehabilitation for children with head injury. The trends suggest that more comprehensive care may lead to better outcomes.