Moshe Feinsod

Preliminary evidence for a beneficial effect of low‐frequency, repetitive transcranial magnetic stimulation in patients with major depression and schizophrenia

This study was designed to evaluate the potential efficacy of repetitive transcranial magnetic stimulation (rTMS) at low‐frequency in patients with major depression and schizophrenia. Experimental Design: We investigated the therapeutic effect of a course of 10 rTMS sessions in 14 subjects with major depression (MD) and 10 with schizophrenia. Principal Observations: Seven of the depressed patients reported significant improvement in depressive symptomatology, and seven of the schizophrenic subjects reported amelioration of anxiety and restlessness. Conclusions: These preliminary results suggest that low‐frequency rTMS may be beneficial mainly in MD and to some extent in schizophrenia, and support the need for controlled studies to further validate its therapeutic potential. Depression and Anxiety 7:65–68, 1998.

Diffuse axonal injury: analysis of 100 patients with radiological signs.

One hundred patients with head injuries who showed diffuse axonal injury on computed tomographic scans are reported. Evaluation of the Glasgow Coma Score, pupillary signs, and computed tomographic findings on admission led to an improved ability to forecast outcomes. Our relatively good results as compared with other series, can be explained by the high proportion of children and by the liberal use of computed tomography to evaluate head injuries, thus revealing that concussion may sometimes be regarded as an early form of diffuse axonal injury.

Non-Hodgkin's lymphoma presenting with spinal epidural involvement

Cord compression was noted at presentation in 10 of 453 (2.2%) previously untreated non‐Hodgkins lymphoma patients seen at the Northern Israel Oncology Center between 1968 and 1983. A prodromal phase of local back pain occurred in eight patients, persisting up to 1 year, followed by a second phase of rapidly progressive signs of cord compression. Five of the ten patients presented with primary spinal epidural involvement (Stage IE), whereas the others had Stage IIE and IIIE (one patient each) and Stage IV, with bone and bone marrow involvement (three patients). All patients had unfavorable histologic diagnoses, mostly of the intermediate grade malignancy types according to the Working Formulation. The patients were treated by radiotherapy (two patients), chemotherapy (three patients), or both modalities (five patients). Seven of the ten patients achieved complete remission, but four of them have subsequently had relapses (two patients in bone, one in central nervous system, and one in mediastinum). The 5‐year actuarial survival and 3‐year relapse‐free survival were 66% and 32%, respectively. Median survival has not been reached after a mean follow‐up of 34 months. Non‐Hodgkins lymphoma with spinal epidural involvement at presentation is an aggressive disease. An intensive treatment combining irradiation with chemotherapy, and surgery as needed, is suggested in order to achieve good local response and long‐term survival.

Brain Natriuretic Peptide and Cerebral Vasospasm in Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE Hyponatremia has been shown in association with cerebral vasospasm (CVS) following aneurysmal subarachnoid hemorrhage (SAH). In the past few years there has been increasing evidence that brain natriuretic peptide (BNP) is responsible for natriuresis after SAH. The purpose of the present study was to investigate the relationship between BNP plasma concentrations and CVS after aneurysmal SAH. METHODS BNP plasma concentrations were assessed at 4 different time periods (1 to 3 days, 4 to 6 days, 7 to 9 days, and 10 to 12 days) in 19 patients with spontaneous SAH. BNP plasma levels were investigated with respect to neurological condition, SAH severity on CT, and flow velocities measured by means of transcranial Doppler. RESULTS Thirteen patients had Doppler evidence of CVS; 7 of these had nonsymptomatic CVS. In 6 patients, CVS was severe and symptomatic, with delayed ischemic lesion on CT in 5 of these. CVS was severe and symptomatic in 6 patients, and delayed ischemic lesions were revealed on CT in 5 of these. BNP levels were found to be significantly elevated in SAH patients compared with control subjects (P=0.024). However, in patients without CVS or with nonsymptomatic CVS, BNP concentrations decreased throughout the 4 time periods, whereas a 6-fold increase was observed in patients with severe symptomatic CVS between the first and the third periods (P=0.0096). A similar trend in BNP plasma levels was found in patients with severe SAH compared with those with nonvisible or moderate SAH (P=0.015). CONCLUSIONS In conclusion, our results show that BNP plasma levels are elevated shortly after SAH, although they increase markedly during the first week in patients with symptomatic CVS. The present findings suggest that secretion of BNP secretion after spontaneous SAH may exacerbate blood flow reduction due to arterial vasospasm.

Hyperbaric oxygen therapy for reduction of secondary brain damage in head injury: an animal model of brain contusion.

Cerebral contusions are one the most frequent traumatic lesions and the most common indication for secondary surgical decompression. The purpose of this study was to investigate the physiology of perilesional secondary brain damage and evaluate the value of hyperbaric oxygen therapy (HBOT) in the treatment of these lesions. Five groups of five Sprague-Dawley rats each were submitted to dynamic cortical deformation (DCD) induced by negative pressure applied to the cortex. Cerebral lesions produced by DCD at the vacuum site proved to be reproducible. The study protocol entailed the following: (1) DCD alone, (2) DCD and HBOT, (3) DCD and post-operative hypoxia and HBOT, (4) DCD, post-operative hypoxia and HBOT, and (5) DCD and normobaric hyperoxia. Animals were sacrificed after 4 days. Histological sections showed localized gross tissue loss in the cortex at injury site, along with hemorrhage. In all cases, the severity of secondary brain damage was assessed by counting the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and caspase 3-positive cells in successive perilesional layers, each 0.5 mm thick. Perilesional TUNEL positive cells suggested the involvement of apoptosis in group 1 (12.24% of positive cells in layer 1). These findings were significantly enhanced by post-operative hypoxia (31.75%, p < 0.001). HBOT significantly reduced the severity and extent of secondary brain damage expressed by the number of TUNEL positive cells in each layer and the volume of the lesion (4.7% and 9% of TUNEL positive cells in layer 1 in groups 2 and 4 respectively, p < 0.0001 and p < 0.003). Normobaric hyperoxia also proved to be beneficial although in a lesser extent. This study demonstrates that the vacuum model of brain injury is a reproducible model of cerebral contusion. The current findings also suggest that HBOT may limit the growth of cerebral contusions and justify further experimental studies.

The association between skull fracture, intracranial pathology and outcome in pediatric head injury

We prospectively studied 653 consecutive head-injured children (less than or equal to 14 years old) treated over a 54-month period (1984-88) at the Department of Neurosurgery of the Rambam Medical Center (Haifa, Israel). Demographic and clinical data were collected, the patients were divided into five age groups (birth to 2 years, 169; 3-5 years, 194; 6-9 years, 164; 10-12 years, 77; and 13-14 years, 49), and the information relative to each was then compared. All patients (except three who died on the operating table) underwent computed tomography (CT) scans; 225 (34.6%) had intracranial pathology, e.g. focal mass lesions, diffuse axonal injury, and subarachnoid haemorrhage. The rate of detected pathology increased with age. Skull fracture was documented in 468 (72%) patients. Craniotomies were done on 114 (17.5%) patients. After 3 months, the patients were classified as having good recovery (84.8%), moderate disability (5.5%), or severe disability (2.3%); 0.9% were in a vegetative state. The mortality was 6.6% (43 patients); of these, 39 (90.7%) had admission Glasgow Coma Scale scores below 8. In our area the annual incidence of neurosurgical hospitalization due to head injury in the pediatric group was 37.6 per 100,000 inhabitants per year. This study substantiates the findings of other series on the effects of prognosis of factors such as associated trauma, admission Glasgow Coma Score, mass lesions with persistent intracranial pressure elevation, or diffuse axonal injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Lithium at therapeutic concentrations inhibits human brain noradrenaline-sensitive cyclic AMP accumulation

Lithium at a therapeutically effective concentration of 1 mM caused significant inhibition of the rise in cyclic AMP induced by noradrenaline in fresh surgically-obtained slices of human brain.

Evaluation of the apoptosis-related proteins of the BCL-2 family In the traumatic penumbra area of the rat model of cerebral contusion, treated by hyperbaric oxygen therapy: a quantitative immunohistochemical study

The growth and progression of traumatic brain injury (TBI) lesions depend significantly on developments in the traumatic penumbra area, perilesional region, where delayed neuronal death occurs. Recent data supports the important role of apoptosis in delayed cell death in TBI. Previously we demonstrated a significant reduction of apoptosis in traumatic penumbra in animals treated by hyperbaric oxygen (HBO).In this study we evaluate the expression of apoptosis-related proteins of the Bcl-2 family (Bcl-2, Bax and Bcl-xL) in the traumatic penumbra area in correlation with the extent of apoptosis in the rat model of focal cerebral contusion, treated by HBO. Sprague-Dawley rats underwent cortical dynamic deformation, some with subsequent hypoxemia. A group of both hypoxemic and non-hypoxemic animals was treated by HBO. The pathological study was based on immunohistochemical staining of the brain sections for Bcl-2, Bax and Bcl-xL with quantitative evaluation of staining by image analysis. The expression of Bcl-2 in hypoxemic animals was lower than in non-hypoxemic animals, but a significant increase in Bcl-2 expression was seen in both groups after HBO treatment. Bcl-xL also demonstrated an increase after HBO treatment but less significant. Staining for Bax protein did not demonstrate significant change after treatment. These data correlate well with the reduction of TUNEL-positive cells in traumatic penumbra after HBO treatment. We concluded that the apoptotic mechanisms are important in delayed cell death in TBI and that post-traumatic hypoxemia increases the intensity of apoptosis, probably through a decrease in Bcl-2 and Bcl-xL expression which normally repress apoptosis. The beneficial effect of HBO treatment in our model of brain contusion correlates well with the increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) following treatment and the appropriate decrease in the extent of apoptosis. In light of these results, the usage of HBO is justified as neuroprotective treament in TBI.

Motor and somatosensory conduction in cervical myelopathy and radiculopathy.

Study Design. Motor and sensory conduction times were measured in patients with cervical myelopathy and radiculopathy. The results were compared with those of control subjects. Objective. To evaluate the clinical value of the combined use of motor-evoked potentials with F wave recording and somatosensory-evoked potentials in cervical myelopathy and radiculopathy. Summary of Background Data. Electromyography and somatosensory-evoked potentials provide only indirect information on the motor pathways. The development of magnetic transcranial stimulation has provided a direct and reliable physiologic insight into the motor system. Methods. Magnetic stimulation of the motor cortex and nerve roots with F wave recording was used to assess central and peripheral motor conduction times. Somatosensory conduction was evaluated by somatosensory-evoked potentials. Results. Significant prolongation of the central sensory and motor conduction times was found in the group with myelopathy. These findings were much more pronounced in patients who had multiple level spondylotic stenosis of the spinal canal than in those harboring a single disc herniation compressing the spiral cord. In Contrast to somatosensory-evoked potentials, motor-evoked potentials combined with F wave recording showed marked Impairment of peripheral conduction. In patients with radiculopathy. Conclusion. Motor-evoked potentials associated with F wave recording was suitable for the evaluation of patients with radiculopathy, The severity of conduction impairment in patients with myelopathy can be assessed by combined motor-evoked potentials and somatosensory-evoked potentials.

Basilar Vasospasm Following Spontaneous and Traumatic Subarachnoid Haemorrhage: Clinical Implications

Summary.Summary. Background: Cerebral vasospasm has been commonly described following subarachnoid haemorrhage (SAH) though its impact on neurological outcome, especially in head trauma, has not been yet elucidated. The purpose of this study was to monitor and correlate neurological condition and flow velocities (FVs) in the arteries of the brain after SAH and more particularly to investigate the influence of basilar artery (BA) vasospasm on neurological outcome. Methods: Daily transcranial Doppler (TCD) evaluations were conducted in 116 consecutive patients with subarachnoid haemorrhage. SAH was of traumatic origin (tSAH) in 59 patients and spontaneous (sSAH) in 57 patients. Vasospasm in the MCA and ACA was defined by a mean FV exceeding 120 cm/s and three times the mean FV of the ipsilateral ICA. Basilar artery (BA) vasospasm was defined as moderate whenever the FV was higher than 60 cm/s and severe above 85 cm/s. Findings: Sixty-two patients (53.4%) had elevated FVs in the BA, among these 34 (29.3%) had FVs above 85 cm/s. Basilar vasospasm was significantly more common in tSAH (59.7%) than in sSAH (40.3%, P=0.041). In patients with moderate and severe BA vasospasm, FVs in the BA increased on the third day after admission and remained elevated for a week before returning to normal value by the end of the second week. This elevation in BA FVs in patients with BA vasospasm was followed by a significant and progressive worsening in the neurological condition at the end of the first week. Permanent neurological deficit was associated with elevated BA FVs consistent with moderate BA vasospasm whereas patients who remained in persistent vegetative state, had FVs consistent with severe BA vasospasm (P=0.00019). Interpretation: The present results further support that BA vasospasm may act as an independent factor of ischaemic brain damage following SAH, especially in head trauma.