Cesare Arienta

Central and peripheral components of writing critically depend on a defined area of the dominant superior parietal gyrus

Classical neuropsychological models of writing separate central (linguistic) processes common to oral spelling, writing and typing from peripheral (motor) processes that are modality specific. Damage to the left superior parietal gyrus, an area of the cortex involved in peripheral processes specific to handwriting, should generate distorted graphemes but not misspelled words, while damage to other areas of the cortex like the frontal lobe should produce alterations in written and oral spelling without distorted graphemes. We describe the clinical and neuropsychological features of a patient with combined agraphia for handwriting and typewriting bearing a small glioblastoma in the left parietal lobe. His agraphia resolved after antiedema therapy and we tested by bipolar cortical stimulation his handwriting abilities during an awake neurosurgical procedure. We found that we could reversibly re-induce the same defects of writing by stimulating during surgery a limited area of the superior parietal gyrus in the same patient and in an independent patient that was never agraphic before the operation. In those patients stimulation caused spelling errors, poorly formed letters and in some cases a complete cessation of writing with minimal or no effects on oral spelling. Our results suggest that stimulating a specific area in the superior parietal gyrus we can generate different patterns of agraphia. Moreover, our findings also suggest that some of the central processes specific for typing and handwriting converge with motor processes at least in the limited portion of the superior parietal gyrus we mapped in our patients.

Shc3 affects human high-grade astrocytomas survival

A selective switch from expression of Shc1 gene to Shc3 occurs with maturation of neuronal precursors into postmitotic neurons. Previous studies showed that in the embryo, Shc1 is maximally expressed in dividing CNS stem cells while it is silenced in mature neurons, where it is replaced by Shc3. Under normal conditions Shc3 is never expressed by glial cells. We now show that in human astrocytomas and glioblastomas, the normal pattern of expression of Shc1/Shc3 is totally subverted, both proteins being present at the same time and in the same cells. Our data indicate that Shc3 is maximally expressed, together with Shc1, in glioblastoma, a highly proliferative tumor with little, if any, indication of neuronal differentiation. In primary cultures of glioblastoma, tumor cells maintain Shc1 expression but downregulate Shc3. Analysis of the phosphorylation status of Shc3 in human glioblastoma tumor samples in vivo indicates that it is tyrosine phosphorylated. Finally, we found that the expression of truncated variants of Shc3 with dominant-negative effects in human high-grade glioma cells that maintain Shc3 expression in vitro leads to a decreased Akt posphorylation and increased apoptosis, thus resulting in impaired survival of the transfected cells. These data suggest that Shc molecules play an important role in glioblastoma cell growth and survival.

Adjuvant Temozolomide Chemotherapy for Treatment of Papillary Tumor of the Pineal Region

BACKGROUND We present a personal case of papillary pineocytoma in a 42-year-old woman. METHODS The lesion was first treated surgically both for diagnostic aims and for resolution of the mass effect causing hydrocephalus and correlated neurological disturbances. Because the tumor recurred after surgery and radiotherapy, we decided to further treat the patient with chemotherapy, in particular with temozolomide. RESULTS Currently, almost 9 years after the first treatment, the patient is symptom-free and follow-up magnetic resonance imaging shows no tumor recurrence. CONCLUSION Although surgery should be considered the first-choice therapy, we think that temozolomide can be a valid option in case of recurrence of these rare tumors.

Spontaneous cervical (C1-C2) cerebrospinal fluid leakage repaired with computed tomography-guided cervical epidural blood patch.

To the Editor: Intracranial hypotension syndrome (IHS) is often caused by persistent cerebrospinal fluid (CSF) leakage. IHS usually presents with orthostatic headache, exacerbated by an increase in intracranial pressure, but other symptoms can be present such as nausea, vomiting, dizziness, neck pain, and paresis of the VIth cranial nerve. It can be spontaneous or related to a trauma, such as dural puncture or surgery, or medical causes such as dehydration. Thanks to improvements in neuroradiological imaging quality, magnetic resonance imaging (MRI) diagnosis of IHS is now more common and easier. IHS is a benign condition, often treated conservatively. If it does not resolve by itself, it usually can be treated with epidural blood patch (EBP), even if a Cochranemeta-analysis showed a lack of randomized controlled trials that confirm the efficacy of this approach. Rarely, IHS is caused by a high cervical problem and, to our knowledge, in the literature there are only three cases of C2 leakage treated with EBP with a large volume of blood (the authors repeated the procedure twice, with 10 mL each time). Case

EDG3 and SHC3 on chromosome 9q22 are co-amplified in human ependymomas

By qPCR we found that EDG3 and SHC3 were amplified in 60% of ependymomas but none in choroid plexus papillomas. In ependymomas EDG3 and SHC3 amplification increased Shc3 protein levels while EDG3 was less affected. Both proteins were co-immunoprecipitated from ependymoma and Shc3 was tyrosine phosphorylated thus presumably active. We showed by digestion with N-glycosidase-F that EDG3 was glycosylated indicating that EDG3 protein was not retained in the endoplasmic reticulum. The co-immunoprecipitation of Shc3 and EDG3 proteins from ependymomas with amplification of SHC3 and EDG3 genes suggests that the two proteins co-operate and are important for ependymomas in vivo.

Acute brainstem dissection of syringomyelia associated with cervical intramedullary neurinoma

Intramedullary tumors and syringomyelia typically present with slowly progressing deficits. More rarely, they are characterized by acute presentation or worsening, at times mimicking other more common etiologies. The acute onset of syringomyelia is most likely attributable to an acute increase in cerebrospinal fluid and epidural venous pressure that results in impulsive fluid movement and, ultimately, in the rupture of the syrinx and dissection into the spinal cord or brainstem. Reported here is a case of acute presentation of a small cervical intramedullary neurinoma due to the upward dissection of its associated syrinx. Critical questions are: (1) how can a small tumor produce a large syrinx? and (2) in the absence of craniospinal interferences, which mechanism underlies the acute expansion of the cavity, resulting in a rapid onset? The authors examined the pathophysiology of syrinx formation and enlargement in intramedullary tumors and reviewed the literature, emphasizing the relationship between spinal cord movements and intramedullary pressure. On the basis of current pathogenetic concepts, the authors concluded that tumor-related syringomyelia might be caused by an association of mechanisms, both from within (obstruction of perivascular spaces; increase in extracellular fluid viscosity due to the tumor itself; intramedullary pressure gradients among different cord levels and between the cord and the subarachnoid space) and from without (the cerebrospinal fluid entering the tissue). All these factors may be amplified, as in the reported case, by a tumor located dorsally at the cervical level. Abnormal postures of the spine, such as a prolonged and excessive flexed neck position, may ultimately contribute to the acute dissection of the syrinx.