H3F3A K27M mutations in thalamic gliomas from young adult patients.

INTRODUCTION: Mutations in H3F3A, which encodes histone H3.3, commonly occur in pediatric glioblastoma. Additionally, H3F3A K27M substitutions occur in gliomas that arise at midline locations (eg, pons, thalamus, spine); moreover, this substitution occurs mainly in tumors in children and adolescents. Here, we sought to determine the association between H3F3A mutations and adult thalamic glioma. METHODS: Genomic H3F3A was sequenced from 20 separate thalamic gliomas. Additionally, for 14 of the 20 gliomas, 639 genes--including cancer-related genes and chromatin-modifier genes--were sequenced, and the Infinium HumanMethylation450K BeadChip was used to examine DNA methylation across the genome. RESULTS: Of the 20 tumors, 18 were high-grade thalamic gliomas, and of these 18, 11 were from patients under 50 years of age (median age, 38 y; range, 17-46), and 7 were from patients over 50 years of age. The H3F3A K27M mutation was present in 10 of the 11 (91%) younger patients and absent from all 7 older patients. Additionally, H3F3A K27M was not detected in the 2 diffuse astrocytomas. Further sequencing revealed recurrent mutations in TP53, ATRX, NF1, and EGFR. Gliomas with H3F3A K27M from pediatric or young adult patients had similar, characteristic DNA methylation profiles. In contrast, thalamic gliomas with wild-type H3F3A had DNA methylation profiles similar to those of hemispheric glioblastomas. CONCLUSION: We found that high-grade thalamic gliomas from young adults, like those from children and adolescents, frequently had H3F3A K27M.

Improved outcome of patients with severe thalamic hemorrhage treated with cerebrospinal fluid drainage and neurocritical care during 1990-1994 and 2005-2009.

INTRODUCTION: Patients with thalamic hemorrhage, depressed level of consciousness and/or signs of elevated intracranial pressure may be treated with neurocritical care (NCC) and external ventricular drainage (EVD) for release of cerebrospinal fluid. METHODS: Forty-three patients with thalamic hemorrhage treated with NCC from 1990 to 1994 (n = 21) and from 2005-2009 (n = 22) were evaluated. Outcome was assessed using the Glasgow Coma Scale (GCS) score at discharge from our unit and the modified Rankin Scale (mRS) for long-term outcome. RESULTS: Patients' age was 59.5 ± 7 years in 1990-1994, and 58.2 ± 9 years in 2005-2009. The median (25th and 75th percentile) GCS score on admission for the two time periods was 9 (6-12) and 9 (4-14), respectively. Long-term follow-up was assessed at a mean of 37.1 (range 19-65) months after disease onset for the 1990-1994 cohort and at 37.4 (range 14-58) months for the 2005-2009 cohort. Compared to patients from 1990 to 1994, patients from 2005 to 2009 had a significantly better outcome (median mRS [25th and 75th percentile]: 5 [4-6] vs. 4 [2-4.5]; p < 0.01). Most patients (13/21, 62 %) treated from 1990 to 1994 had unchanged or lower GCS scores during their NCC stay in contrast to 7/22 (32 %) from 2005 to 2009. At the last follow-up, 13/21 (62 %) patients from 1990 to 1994 were dead in comparison to 4/21 (19 %) from 2005 to 2009 (p < 0.05). Negative prognostic factors were the 120 h post-admission GCS score in the 1990-1994 patient cohort (p = 0.07) and high age in the recent cohort (p = 0.04). CONCLUSIONS: Patients with thalamic hemorrhage and depressed level of consciousness on admission had a worse outcome in the early 1990s compared with the late 2000s, which may at least be partially attributed to refined neurocritical care.

Glasgow Coma Scale and hematoma volume as criteria for treatment of putaminal and thalamic intracerebral hemorrhage.

BACKGROUND: The decision to administer conservative or surgical treatment for putaminal and thalamic ICH is still a controversial issue. This study was undertaken to examine the decision-making criteria for these 2 treatments. METHODS: In a retrospective study, case records of 400 patients with spontaneous putaminal and thalamic hemorrhage who underwent conservative treatment (n = 201) and surgical treatment (n = 199) over the past 5 years were examined. Conservative treatment included hypertonic solution treatment and hypertension control. Surgical treatments included endoscopic surgery, craniotomy, and stereotactic aspiration. Preoperative GCS score and ICH volume were the major evaluating factors, and comparison of the 30-day mortality rate and 6-month BI score was used for outcome evaluation. RESULTS: In patients with a GCS score of 13 to 15, there was no difference in mortality between conservative and surgical treatments. At a GCS score of 9 to 12 and ICH volume of less than 30 mL, the mortality rate with surgical treatment (10.5%) was lower than that with conservative treatment (20.0%, P < .05). At a GCS score of 3 to 8 and ICH volume of at least 30 mL, surgical treatment was for life saving. Mortality rates were lower for conservative treatment than for surgical treatment when the GCS score was 3 to 12 and ICH volume less than 30 mL. Endoscopic surgery had a better functional outcome compared with craniotomy and stereotactic aspiration when the GCS score was at least 9 (P < .001 and P < .02, respectively). Those in conservative treatment received a better BI score than those in surgical treatment did when the ICH volume was less than 40 mL (P < .001). CONCLUSIONS: Intracerebral hemorrhage volume is probably more important than GCS score in determining treatment. Our nonrandomized data could be interpreted to show that conservative treatment is suggested at GCS score of at least 13 or when ICH volume is less than 30 mL, regardless of GCS score. Surgical treatment could be recommended at GCS score of less than 12 with ICH volume of at least 30 mL for life saving. Endoscopic surgery may improve the functional outcomes because it is less invasive and effectively removes the ICH at GCS score of at least 9.

Surgical resection of thalamic tumors in children: approaches and clinical results.

OBJECTIVES: Thalamic tumors are uncommon, and although gross total removal (GTR) is a prospective goal, its interest is debated because the thalamus constitutes a highly functional region. The relation of choice of the surgical approach, achievability of GTR, and operative morbidity to the anatomic location of the tumor has received little attention in the medical literature. MATERIALS AND METHODS: We reviewed retrospectively the cases of pediatric patients treated for thalamic tumor, with pre- and postoperative magnetic resonance imaging, and who were operated with the aim of maximal surgical removal. CONCLUSION: We reviewed 16 cases operated between 1992 and 2003. The clinical presentation was dominated by intracranial hypertension and hemiparesis. Fifteen children were operated through transcortical approaches: transfrontal in six cases, transparietal in six, and transtemporal in three. The remaining patient was operated through an infratemporal approach. All operations performed since 1998 used intraoperative neuronavigation. Complete or near-total resection was achieved in 11 cases; only subtotal resection was achieved in the remaining five cases. The most common postoperative morbidity was visual field defect. Hemiparesis was unchanged or improved in all the cases. Seven children died of tumor progression, in relation with high histological grade, and one died of acute hydrocephalus. The approach to thalamic tumors needs to be planned according to the location of critical neural structures. GTR of thalamic tumors in children bears acceptable morbidity and may even improve preoperative deficits. Surgery alone can be curative in low-grade tumors; in high-grade or infiltrating tumors, GTR is only part of the overall oncological management.

[Childhood diencephalic pilocytic astrocytoma. A review of seven observations]. / Les astrocytomes pilocytiques du diencephale de l'enfant. à propos de sept observations.

BACKGROUND AND PURPOSE: Pilocytic astrocytoma (PA) is a WHO grade I tumor of the central nervous system mostly arising in children and young adults. Management of diencephalic PA is a difficult challenge. Surgical treatment has to cope with both the difficulties of deep location and eloquent area tumors. MATERIALS AND METHODS: We retrospectively reviewed seven pediatric cases (female: 4, male: 3) of diencephalic PA. Opto-chiasmatic tumors were excluded from the series. Mean age at diagnosis was 108 months (9 years) (range: 4 month-18 years), median age was 111 months. Median follow-up for the series was 125 months. Tumor locations were as followed: right thalamus: 2, both thalami: 1, hypothalamus: 3, and right basal ganglia: 1. At the onset, the first symptom was mostly raised intracranial pressure. The delay in diagnosis ranged from 48 hours up to 6 years. TREATMENT: a shunting procedure was performed in 3 patients, a direct surgical approach in 5 patients (gross total removal: 2; partial removal: 3) and one patient had only a biopsy. Three children were re-operated. Three patients were treated by radiationtherapy (RT) after surgery. Chemotherapy was delivered for 4 children. RESULTS: The overall survival rate was 71.4 months (almost 6 years) (range: 3-184 months). Median survival rate was 42 months (3.5 years). Three children died, two by tumor progression and one death related to late side-effects of RT. Four patients have a good quality of life with GOS I (n = 3) or II (n = 1). We observed tumor regression in two patients at 1 and 17 years after the beginning of treatment. Correct diagnosis was only made for two cases at the initial pathological examination. CONCLUSION: The course of diencephalic PA is still unpredictable. The tumor can be controlled by a partial surgical removal, and a residual tumor can sometimes decrease in size after surgery. Gross total removal of these tumors, although difficult, may be performed. With cranial navigation systems, the risk is low. Pathological diagnosis is sometimes difficult to assess.

Surgical treatment of thalamic hematomas via the contralateral transcallosal approach.

Acute management of deep-seated hematomas remains controversial. Since patients with these hematoma later tend to develop severe edema and necrosis around the lesion, when surgery is indicated it should be done as early as possible. The purpose of this study was to compare whether early surgical removal and conservative treatment of primary thalamic hematoma correlated with improved neurological outcome. Last year, 61 patients with primary thalamic hematomas were admitted to our institution. Of these, 21 underwent surgery via contralateral transcallosal approach during the ultraearly stage (within 6 hours) after the apoplectic attack, and 24 patients were treated conservatively. Another 16 patients were excluded from the study due to systemic disease, mild hematoma (<40 cc), and deep coma associated with absence of brain stem reflexes. Initial Glasgow coma scores (GCS) at admission were similar for operated and nonoperated patients (8.64 +/- 1.93 versus 9.50 +/- 2.10, P>0.05). In the operated group, two patients had good recoveries and returned to normal life (Glasgow Outcome Score, or GOS, I), four had moderate disability and needed partial care (GOS II), six had severe disability and needed nursing care (GOS III), and six had a vegetative state (GOS IV). However, in the nonoperated group, one patient had good recovery and returned to normal life (GOS I), two had moderate disability and needed partial home care (GOS II), three had severe disability and needed nursing care (GOS III), and six had a vegetative state (GOS IV). In this group, the 30-day mortality rate was 50%. Mortality was markedly lower in the operated group (14.3%) than the nonoperated group. and this difference was statistically significant (chi2=3.33, P<0.05). From this study, we believe that evacuation of primary thalamic hematoma via the contralateral transcallosal microsurgical approach may be useful for deciding on the indication and predicting the functional prognosis.

Unilateral thalamic lesions in premature infants: risk factors and short-term prognosis.

The aim of the study was to assess incidence, risk factors, clinical symptomatology and short-term outcome of unilateral thalamic lesions in preterm infants, as detected by ultrasound. Sixteen preterm infants, born after a gestational age of less than 35 weeks, with a unilateral thalamic lesion, but without additional significant cerebral lesions, were included. Their follow-up data were compared to those of a selected control group consisting of healthy premature infants. In addition, the neonatal clinical data of the patients with a thalamic lesion were compared to data of the healthy control group and of a general control group, consisting of a non-selected year-cohort of preterm infants. During the study period, the incidence of unilateral thalamic lesions was 5.3% among preterm infants. Ultrasound was not able to distinguish between hemorrhagic and ischemic lesions. The infants with a unilateral thalamic lesion had a more complicated respiratory course and were ventilated significantly longer than infants without such a lesion. The infants with a thalamic lesion had disturbances in tone, persisting throughout infancy, while the healthy control group showed only transient disturbances in tone.

Perinatal hypoxic-ischemic thalamic injury: clinical features and neuroimaging.

A common pattern of hypoxic-ischemic cerebral injury in the term newborn involves predominantly cerebral cortex and subcortical white matter. We describe 20 term newborns with moderate or severe acute hypoxic-ischemic encephalopathy who exhibit a different pattern of abnormalities on computed tomography, with evidence of decreased tissue attenuation predominantly in thalami and basal ganglia and relative preservation of cerebral cortex and white matter. Profound, acute hypoxic-ischemic insult (eg, umbilical cord prolapse, uterine rupture, or massive placental abruption) was documented in 16 of 20 infants (80%). Characteristic clinical features during the newborn period included irritability, tonic posturing of limbs, and persistent lower cranial nerve dysfunction, often with prominent tongue fasciculations. This pattern of central injury appears to be highly predictive of poor outcome; 7 newborns (35%) died, and all survivors who had follow-up to 18 months of age (11) had major neurological sequelae (eg, spastic quadriplegia, choreoathetosis, and persistent feeding problems). This pattern of hypoxic-ischemic cerebral injury corresponds closely to experimental animal models of "acute total" perinatal asphyxia.

Thalamic tumors in children.

Thalamic tumors (TT) merit individual analysis and must not be confused with tumors that, while involving the entire thalamus have a different origin. We analyzed 26 patients who fulfilled our criteria of having "strictly" TT. We examined incidence, clinical features, histology, response to treatment (mainly surgery), recurrence rate, mortality and prognosis. We considered that histology and surgical treatment were the most important items related to prognosis. Low-grade tumors (LGT) had a good prognosis, while anaplastic tumors (AT) had a discouraging one; nevertheless both must be operated on. We believe that total removal of LGT is curative and total removal of AT, even if it is not curative, can extend survival by some months. Radiotherapy and chemotherapy seemed to be of little value in our series of TT.

Evoked potential studies in thalamic hemorrhage.

Due to paucity of a comprehensive study on somatosensory and motor evoked potentials in thalamic hemorrhage, the present study has been undertaken. Clinical examination, motor evoked potential (MEP) and median somatosensory evoked potential (SEP) studies were performed on 22 consecutive patients with CT-proven thalamic hemorrhage. The clinical and evoked potential studies were carried out on admission and repeated at the end of 3 months. The hematomas were classified as type A (with posterolateral extension) and type B (without posterolateral extension). The hematomas were of type A and type B in 11 patients each. The patients with type A hematomas had persistent inexcitability of motor pathways and SEPs were unrecordable. In type B, MEP was not recordable in three, prolonged in five and normal in three patients; in all these patients, MEP returned to normal in the follow-up study. The cortical potentials of median SEP were normal in four and unrecordable in five patients with type B hematoma. In the follow-up study, SEPs became recordable in all, although central sensory conduction time (CSCT) was prolonged in three patients. MEP and SEPs were related to the respective motor and sensory dysfunction and to posterolateral extension of hematoma. Patients with type A hemorrhage had worse prognosis compared to type B, emphasising the importance of posterolateral extension. A persistently unrecordable MEP and SEP in thalamic hemorrhage suggests a posterolateral extension which predicts a poor outcome.

Low-grade glial tumors in basal ganglia and thalamus: natural history and biological reappraisal.

The natural history of 70 patients affected by low-grade astrocytomas was recorded after the histological diagnosis was obtained by serial stereotactic biopsy. Forty-three percent of these patients died within 3 years. The value of cell kinetics assessment at the time of stereotactic biopsy was investigated, and the labeling index percent may be considered the most accurate prognostic factor in these histologically homogeneous astrocytomas. It has been confirmed that the young age of patients predicts a more favorable course, but the value of this also seems to be linked to and dependent on cell kinetics. These data are discussed in view of the opportunity to perform more aggressive "cytoreductive" treatments in deep brain tumors when these indices support an expected poor prognosis.

Thalamic hemorrhage. 30 cases studied: clinico-tomodensitometric correlations.

The clinico-tomographic correlations in 30 patients hospitalized for primary thalamic hemorrhage were studied. Arterial hypertension, observed in 90% of patients, represented the most important risk factor. Twenty-six subjects showed a sensory-motor hemisyndrome contralaterally to the lesion, nineteen showed alteration in level of consciousness from confusion to stupor and coma. Twelve subjects had poorly reactive pupils and eleven speech disturbances with involvement of the left thalamus. Seven patients died following hemorrhage; all subjects presented ventricular bleeding, severe disturbance of consciousness and arterial hypertension. On admission to hospital impairment of consciousness was the most significant unfavourable prognostic factor.

Los síndromes de lesión talámica

En la unidad de Neurología del Centro Hospitalario San Juan de Dios de Bogotá, durante cuatro años (1986 a 1989), se estudiaron en forma consecutiva 25 pacientes con lesiones talámaticas no fatales. Se registraron los hallazgos neurológicos, neurosicológicos y neurooftalmológicos y los diagnósticos se confirmaron por tomografía computarizada (TC). Fueron 14 mujeres y 11 varones con una edad promedio de 52.5 y un rango de 25 a 84 años. La lesión talámica fue de origen vascular en 24 casos, ocho por infarto isquémico, cuatro por infarto hemorrágico y 12 con hematomas parenquimatosos. Diecisiete pacientes tenían hipertensión arterial sistémica y el único factor de riesgo en otros dos era el consumo de cocaína base (basuco). Ocho infartos se presentaron en el tálamo derecho, 12 en el izquierdo y cinco pacientes tuvieron lesiones bilaterales, uno de ellos con un glioma complobado por biopsia. En 5 pacientes con lesiónes bilateral se observó el síndrome del "Tope" de la arteria basilar, por compromiso del pedículo retromamilar; en todos ellos encontramos alteraciones sensitivomotoras, cerebelosas, oculomotoras bilaterales y demencia. Solamente un paciente presentó el clasicó síndrome de hiperpatía (Dejerine-Roussy). En los restantes se observaron asociaciones de síndromes sensitivomotores, cerebelosos, neurooftalmológicos, neuropsicológicos, y del comportamiento motor que remedan con frecuencia los hallazgos clínicos de la alteración cortical frontal, temporal o parietal.