Patrick Lasala

False localizing signs in upper cervical spinal cord compression

Proprioceptive loss, paresthesias, and atrophy of the hands can occur with disorders afflicting the upper cervical spinal cord. The diagnosis might be erroneous, because compression in this region might produce signs and symptoms that seem to originate in the lower cervical cord. This article reviews the clinical presentation and radiographic data of a consecutive series of 11 patients who presented between 1992 and 1994 with an extradural lesion above the C4 level. Each patient had a characteristic syndrome of finger and hand dysesthesia, hand atrophy, and occipital or cervical pain. These complaints usually preceded the development of spasticity and gait disturbance. Initial diagnoses included brachial plexopathy, shoulder dysfunction, viral syndrome, and cervical spondylosis at a lower segment. Cervical spondylosis or a herniated disc was the most common pathogenesis. The most commonly involved level was C3-C4. Nine patients underwent a surgical procedure; eight showed significant postoperative improvement (mean time of follow-up examination, 9.7 mo; follow-up range, 1-24 mo). One patient was lost to follow-up. Although the pathophysiology of these findings is unknown, theories include anterior spinal artery ischemia, venous obstruction, and differential decussation of the forelimb and hindlimb fibers of the corticospinal tract. Recognition of this syndrome might prevent inappropriate operative intervention in patients with coexisting pathological conditions of the lower cervical spinal cord.

Phase II trial of merbarone in patients with malignant brain tumors.

The standard treatment for patients with primary malignant glioma includes surgical resection, radiotherapy, and nitrosourea. Despite this multimodality approach, adults with newly diagnosed glioblastoma multiforme (GBM) and high-grade astrocytoma have a median survival duration of 50 weeks and 150 weeks respectively. Chemotherapy has had a limited impact on the survival of these patients. Merbarone (5-phenylcarboxamide-2-thiobarbituric acid) is a nonsedating derivative of barbituric acid that crosses the blood brain barrier. Antitumor activity of merbarone has been described against L1210, B16 melanoma cell line and the M5076 sarcoma cells in phase I studies. Merbarone inhibits DNA synthesis and tumor growth by inducing single strand breaks in DNA. It also inhibits RNA and protein synthesis. We evaluated merbarone in a phase II trial in patients (pts) with recurrent or refractory GBM (7 pts) and high grade anaplastic astrocytoma (7 pts). Fourteen patients (nine males, five females) were treated with merbarone at a dose of 1000 mg per m2 per day by continuous intravenous infusion for 5 days every 3 weeks. Every patient received at least two cycles of treatment No complete or partial responses were observed, although one patient had stable disease lasting 20 weeks. Our conclusion is that merbarone is ineffective against GBM and high-grade anaplastic astrocytoma at the dose and schedule in which it was administered in this trial.

Dynamic perfusion MRI characteristics of dural metastases and meningiomas: A pilot study characterizing the first-pass wash-in phase beyond relative cerebral blood volume

OBJECTIVE Dural metastases and meningiomas are extraaxial lesions that may be difficult to distinguish using conventional imaging methods. This distinction, however, is clinically important. Perfusion MRI may play a role in preoperative assessment. The aim of this study was to evaluate the utility of perfusion parameters in differentiating between these two entities. In particular, we evaluated two new metrics that reflect the first-pass wash-in characteristics of perfusion. MATERIALS AND METHODS Patients with intracranial extraaxial masses who underwent perfusion MRI were included. Region-of-interest analysis was performed and several perfusion metrics were calculated including relative cerebral blood volume (rCBV), mean transit time and time to peak (TTP) enhancement from initial bolus enhancement (T0), calculated as TTP-T(0). Two new metrics characterizing first pass wash-in enhancement were also measured: relative wash-in time and wash-in slope. Lesions were divided into two groups: meningioma and metastasis. Comparisons between the two groups were made using Wilcoxon rank sum and Fisher exact tests. RESULTS Twenty lesions were studied (12 meningioma and 8 metastases). Compared with meningiomas, relative wash-in time was statistically lower in metastases (p < 0.05). No other statistically significant differences were observed. Specifically, there was no difference between the two study groups in rCBV. CONCLUSION First-pass wash-in characteristics of dural lesions may be useful for evaluating and characterizing lesions. In particular, a metric describing the wash-in phase of perfusion-that is, relative wash-in time-was found to be lower in metastases compared with meningiomas. Contrary to a prior report, we found rCBV to be limited in the evaluation of extraaxial lesions.

ILAE type 3 hippocampal sclerosis in patients with anti-GAD–related epilepsy

Objective: To describe the neuropathologic findings and clinical course of 2 patients who underwent temporal lobectomy for medically refractive epilepsy and were later found to have high anti–glutamic acid decarboxylase (GAD) concentrations. Methods: Small case series. Results: Neuropathologic examination of both patients revealed International League Against Epilepsy (ILAE) type 3 hippocampal sclerosis. Following surgery, both developed signs and symptoms of stiff person syndrome and later cerebellar ataxia. Laboratory studies demonstrated high concentrations of anti-GAD antibodies in both patients. Conclusions: These cases suggest that ILAE type 3 hippocampal sclerosis may be immunologically related to and may exist as part of a broader anti-GAD–related neurologic syndrome in some instances.

Fractionated stereotactic radiation therapy for brain metastases: a systematic review with tumour control probability modelling

OBJECTIVE Fractionated stereotactic radiotherapy (FSRT) is a relatively new option for the treatment of brain metastases. We performed a quantitative systematic review to determine if local control (LC) following is affected by FSRT dosing regimen. METHODS We reviewed articles describing LC following FSRT for brain metastases. LC data from each study were extracted from actuarial survival curves and aggregated to form a single data set. LC curves were generated using the Kaplan-Meier method. Log-rank testing and Cox proportional hazards modelling were utilized to test for associations between the biologically effective dose (BED) and LC. Tumour control probability modelling was performed to illustrate the relationship between the BED and the likelihood of LC after FSRT. RESULTS 10 studies (720 metastases) met inclusion criteria. Prescription doses ranged from 18 to 42 Gy, delivered in 3-12 fractions (BED range: 29-100 Gy10). 1- and 2-year actuarial LC rates were 80% and 69%, respectively. Increasing BED was associated with improved LC (HR = 0.77 per increase of 10 Gy10, p = 0.009). Tumour control probability models demonstrated that the BEDs of 40, 50 and 60 Gy10 yield predicted 1-year LC rates of 73%, 78% and 84%, respectively. The BEDs of 40, 50 and 60 Gy10 yield 2-year LC rates of 62%, 69% and 81%, respectively. CONCLUSION FSRT provides high rates of LC for patients with brain metastases. We found evidence for a dose-response relationship that should be explored in prospective trials. Advances in knowledge: This review identified a dose-response relationship for LC in patients treated with FSRT for brain metastases.

Electrophysiologic Studies and Intraoperative Localization in a Child with Epilepsia Partialis Continua

A 7-year-old boy with progressively worsening epilepsia partialis continua (EPC) involving the left side of the face was shown to have a small lesion in the right sensorimotor area. Facial twitches were sometimes but not always associated with spikes in the scalp EEG. At operation, electrocorticography (ECoG) showed seizure discharges at two electrodes in a grid with 1-cm spacing, at a site that coincided with the radiologic lesion and an area of abnormal pial vasculature. The gyral pattern suggested that this site was precentral, but cortical somatosensory evoked potential (SSEP) recordings and direct cortical stimulation demonstrated that it was postcentral and a limited resection was performed. The pathologic diagnosis was focal cortical dysplasia. Postoperatively, the child had no neurologic deficits, and seizure activity was reduced by more than 90%.