Administration off label of recombinant factor-VIIa (rFVIIa) to patients with blunt or penetrating brain injury without coagulopathy.

Traumatic brain contusions may increase in size over time or may develop at a delay after injury. This may lead to neurological deterioration, long term morbidity or even death. Coagulation disorders after injury can contribute to progression of haemorrhage. Recombinant activated factor VII (rFVIIa) was used in 12 patients with a severe head injury who had no systemic coagulopathy but who were considered to be at risk of progression of their intracranial lesion. Twelve consecutive patients suffering from life-threatening acute head injuries from blunt (3 cases) and penetrating mechanisms were given with rFVIIa, either to prevent the expected development of brain contusion or to assist in bleeding control during surgery. In 11 patients, rFVIIa was given by the attending neurosurgeon. Two of the patients died of their severe penetrating injuries one of whom had severe vasospasm 2 days after administration of rFVIIa. The other 11 patients did not appear to suffer any treatment-related adverse effects. When the drug was given prophylactically to prevent brain resection (6 cases) or to limit the need for widening resection (5 cases), marked control was achieved in seven cases, and a lesser effect was observed in the other 4 cases. We conclude that, in a small and highly individually selected series of patients with severe head injury, the administration of rFVIIa did not lead to adverse effects. Although the majority of patients were considered to be at high risk of progression of their lesions, this occurred in only one. The early use of rFVIIa in head injured patients without systemic coagulopathy may reduce the occurrence of enlargement of contusions, the requirement of further operation, and adverse outcome. Prospective randomised controlled studies are required to investigate this.

The effect of oxygenation level on cerebral post-traumatic apoptotsis is modulated by the 18-kDa translocator protein (also known as peripheral-type benzodiazepine receptor) in a rat model of cortical contusion.

AIMS: Hyperbaric hyperoxia has been shown to reduce apoptosis in brain injury. As the 18-kDa translocator protein (TSPO), also known as peripheral-type benzodiazepine receptor, is closely associated with the mitochondrial transition pore and because of its role in mitochondrial respiration and apoptosis, we hypothesized that reduction of apoptosis by hyperoxia may involve the TSPO. METHODS: TSPO and transferase-mediated dUTP nick end labelling (TUNEL) immunopositivity was first assessed in cortical contusion, created by dynamic cortical deformation, by immunohistochemistry in rats exposed to normoxia [(dynamic cortical deformation (DCD)], normobaric hyperoxia or hyperbaric hyperoxia [hyperbaric oxygen therapy (HBO)]. In a second step, transmembrane mitochondrial potential (Deltapsi(M)) and caspase 9 activity were assessed in the injured area in comparison with the noninjured hemisphere. Measurements were performed in DCD and HBO groups. A third group receiving both HBO and the TSPO ligand PK11195 was investigated as well. RESULTS: TSPO correlated quantitatively and regionally with TUNEL immunopositivity in the perilesional area. Hyperoxia reduced both the number of TSPO expressing and TUNEL positive cells in the perilesional area, and this effect proved to be pressure dependent. After contusion, we demonstrated a dissipation of Deltapsi(M) in isolated mitochondria and an elevation of caspase 9 activity in tissue homogenates from the contused area, both of which could be substantially reversed by hyperbaric hyperoxia. This protective effect of hyperoxia was reversed by PK11195. CONCLUSIONS: The present findings suggest that the protective effect of hyperoxia may be due to a negative regulation of the proapoptotic function of mitochondrial TSPO, including conservation of the mitochondrial membrane potential.

Comparison of moderate hyperventilation and mannitol for control of intracranial pressure control in patients with severe traumatic brain injury--a study of cerebral blood flow and metabolism.

OBJECTIVE: To compare the respective effects of established measures used for management of traumatic brain injury (TBI) patients on cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGlc) and lactate (CMRLct). METHODS: Thirty-six patients suffering from severe traumatic brain injury (TBI) were prospectively evaluated. In all patients baseline assessments were compared with that following moderate hyperventilation (reducing PaCO2 from 36 +/- 4 to 32 +/- 4 mmHg) and with that produced by administration of 0.5 gr/kg mannitol 20% intravenously. Intracranial and cerebral perfusion pressure (ICP, CPP), CBF and arterial jugular differences in oxygen, glucose and lactate contents were measured for calculation of CMRO2, CMRGlc and CMRLct. RESULTS: Following hyperventilation, CBF was significantly reduced (P < 0.0001). CBF remained most often above the ischemic range although values less than 30 ml x 100 gr(-1) x min(-1) were found in 27.8% of patients. CBF reduction was associated with concurrent decrease in CMRO2, anaerobic hyperglycolysis and subsequent lactate production. In contrast, mannitol resulted in significant albeit moderate improvement of cerebral perfusion. However, administration of mannitol had no ostensible effect either on oxidative or glucose metabolism and lactate balance remained mostly unaffected. CONCLUSIONS: Moderate hyperventilation may exacerbate pre-existing impairment of cerebral blood flow and metabolism in TBI patients and should be therefore carefully used under appropriate monitoring. Our findings rather support the use of mannitol for ICP control.

Hyperbaric oxygen therapy reduces neuroinflammation and expression of matrix metalloproteinase-9 in the rat model of traumatic brain injury.

The acute inflammatory response plays an important role in secondary brain damage after traumatic brain injury (TBI). Neutrophils provide the main source of matrix metalloproteinases (MMPs) which also play a deleterious role in TBI. Numerous preclinical studies have suggested that hyperbaric oxygen therapy (HBOT) may by beneficial in various noncerebral and cerebral inflammatory diseases. The goal of this study was to evaluate the effects of HBOT on inflammatory infiltration and the expression of MMPs in correlation with secondary cell death in the rat model of dynamic cortical deformation (DCD). Twenty animals underwent DCD with subsequent HBOT (2.8 ATA, two sessions of 45 min each); 10 animals: DCD and normobaric oxygenation (1 ATA), 10 animals: not treated after DCD. Cell death was evaluated by TUNEL. Neutrophils were revealed by myeloperoxidase staining. Immunohistochemical staining for MMP-2 and -9 and tissue inhibitors of MMP-1 (TIMP-1) and -2 was also performed and the results were quantitatively evaluated by image analysis. In the animals treated by HBOT, a significant decrease in the number of TUNEL-positive cells and neutrophilic inflammatory infiltration was seen in comparison with nontreated animals and those treated by normobaric oxygen. The expression of MMP-9 was also significantly lower in the treated group. Staining for MMP-2 and TIMP-2 did not change significantly. Our results demonstrate that HBOT decreased the extent of secondary cell death and reactive neuroinflammation in the TBI model. The decline of MMP-9 expression after HBOT may also contribute to protection of brain tissue in the perilesional area. Further research should be centred on the evaluation of long-term functional and morphological results of HBOT.

Alteration in brain natriuretic peptide (BNP) plasma concentration following severe traumatic brain injury.

BACKGROUND: Brain natriuretic peptide (BNP) is a potent natriuretic and vasodilator factor which, by its systemic effects, can decrease cerebral blood flow (CBF). In aneurysmal subarchnoid hemorrhage (aSAH), BNP plasma concentrations were found to be associated with hyponatremia and were progressively elevated in patients who eventually developed delayed ischemic deficit secondary to vasospasm. The purpose of the present study was to evaluate trends in BNP plasma concentrations during the acute phase following severe (traumatic brain injury) TBI. METHODS: BNP plasma concentration was evaluated in 30 patients with severe isolated head injury (GCS<8 on admission) in four time periods after the injury (period 1: days 1-2; period 2: days 4-5; period 3: days 7-8; period 4: days 10-11). All patients were monitored for ICP during the first week after the injury. FINDINGS: The initial BNP plasma concentrations (42+/-36.9 pg/ml) were 7.3 fold (p<0.01) higher in TBI patients as compared to the control group (5.78+/-1.90 pg/ml). BNP plasma concentrations were progressively elevated through days 7-8 after the injury in patients with diffused SAH as compared to patients with mild or no SAH (p<0.001) and in patients with elevated ICP as compared to patients without elevated ICP (p<0.001). Furthermore, trends in BNP plasma concentrations were significantly and positively associated with poor outcome. INTERPRETATION: BNP plasma concentrations are elevated shortly after head injury and are continuously elevated during the acute phase in patients with more extensive SAH and in those with elevated ICP, and correlate with poor outcomes. Further studies should be undertaken to evaluate the role of BNP in TBI pathophysiology.

Comparative overview of brain perfusion imaging techniques.

Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are: Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Xenon-enhanced Computed Tomography (XeCT), Dynamic Perfusion-computed Tomography (PCT), Magnetic Resonance Imaging Dynamic Susceptibility Contrast (DSC), Arterial Spin-Labeling (ASL), and Doppler Ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow (CBF) or volume (CBV). All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview, established by consensus among specialists of the various techniques. For clinicians, this paper should offers a clearer picture of the pros and cons of currently available brain perfusion imaging techniques, and assist them in choosing the proper method in every specific clinical setting.

Role of brain natriuretic peptide in cerebral vasospasm.

BACKGROUND: Brain natriuretic peptide (BNP) is a potent natriuretic factor responsible for hyponatremia observed in patients with SAH. Through its systemic effects (reduction of blood volume and blood pressure) BNP may augment cerebral blood flow reduction and ischemia secondary to vasospasm. The purpose of the present study was to evaluate the relationship between BNP plasma concentration during the first 12 days following SAH and the development of cerebral vasospasm (CVS). The authors propose a hypothesis for the role played by natriuretic peptides in the pathophysiology of cerebral vasospasm based on the present findings and review the literature. METHODS: Thirty eight patients with spontaneous SAH were prospectively included in the present study. BNP plasma concentrations were assessed at four different time periods following SAH (day 1-3, 4-6, 7-9, 10-12). TCD evidence of CVS was found in 26 patients (68.5%), fourteen patients (36.8%) had delayed ischemic neurological deficits (DIND). FINDINGS: Initial BNP plasma concentrations were significantly more elevated in patients who eventually did not develop DIND (95.07+/-107.65 pg/ml vs. 25.81+/-22.57 pg/ml, p=0.0053). However, in patients with DIND, the BNP plasma concentration increased by 3.69 ( p<0.05), 5.89 ( p<0.001) and 4.54 fold ( p<0.001) between days 1-3 to days 4-6, 7-9 and 10-12 respectively (day 1 was regarded as the day of hemorrhage). In patients without CVS or asymptomatic CVS the BNP plasma concentration decreased between days 1-3 to day 10-12. A similar trend in BNP plasma concentration was found in patients with severe SAH (Fisher's score 3-4) as compared with patients with non visible or moderate SAH (BNP concentration ratio day 7-9/1-3: 4.37 vs. 0.75, p=0.015; day 10-12/1-3: 3.37 vs. 0.3, p=0.0144). The trend in BNP plasma concentration between day 1-3 to day 7-9 was found to correlate with CVS severity with an average increase of 2.01, 3.8 and 5.44 fold for mild, moderate and severe VS respectively ( p<0.01, r=0.4174). INTERPRETATION: These results suggest that BNP secretion in SAH patients is closely related to the bleeding intensity and vasospasm severity as well as to development of DIND with a progressive and marked increase during the clinical course in patients who eventually develop cerebral ischemia. Taken together the local and systemic effects of BNP on CBF suggest that BNP might play a role in the pathophysiology of CVS through its systemic effects on blood pressure and plasma volume BNP leading to an aggravation of brain ischemia secondary to vasospasm.

Assessment of cerebral blood flow by means of blood-flow-volume measurement in the internal carotid artery: comparative study with a 133xenon clearance technique.

BACKGROUND AND PURPOSE: We sought to evaluate a new, angle-independent ultrasonic device for assessment of blood flow volume (BFV) in the internal carotid artery (ICA). METHODS: Nineteen patients and 4 healthy volunteers were enrolled in a comparative study conducted in the Care Unit of the Division of Neurosurgery at UCLA Medical Center. All patients had been admitted because of severe brain injury: 15 patients with severe head trauma (Glasgow Coma Scale score< or =8) and 4 patients with subarachnoid hemorrhage due to aneurysm rupture. In all patients and subjects, cerebral blood flow (CBF) values obtained with the 133xenon-clearance technique were compared with BFV measurements in the ipsilateral ICA. RESULTS: Hemispheric CBF values showed a close and linear correlation with BFV measurements (r=0.76, P<0.0001). Global CBF values showed a higher correlation with the total BFV value obtained from both ICAs (r=0.84, P<0.0001). With 37 mL x min(-1) x 100 g(-1) as a cutoff value for the ischemic range, a BFV value of 220 mL/min would yield a positive predictive value of 91.7% and a negative predictive value of 82.6% (sensitivity 73.3%, specificity 95%). Conversely, BFV sensitivity and specificity were 60% and 96%, respectively, for the hyperemic range defined by a CBF value >55 mL x min(-1) x 100 g(-1) (positive predictive value of 85.7% and negative prediction value of 85.7%). CONCLUSIONS: BFV measurements with this new technology proved to accurately correlate with CBF values evaluated by the 133xenon-clearance technique. These results support the implementation of this technique for bedside assessment of cerebral hemodynamics in critically ill neurosurgical patients.

Basilar vasospasm following spontaneous and traumatic subarachnoid haemorrhage: clinical implications.

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.

Excitatory and inhibitory corticospinal responses to transcranial magnetic stimulation in patients with minor to moderate head injury.

OBJECTIVES: The changes in excitatory and inhibitory responses to transcranial magnetic stimulation (TMS), as attested by motor evoked potential (MEP) and silent period (SP) parameters, were compared in patients who sustained minor to moderate head injury. METHODS: A total of 38 patients with brain concussion, and diffuse, focal, and combined brain injury and 20 healthy volunteers were examined. The MEPs and SPs were recorded from the abductor pollicis brevis muscle after single pulse TMS 2 weeks after head trauma. The parameters assessed were the MEP resting threshold, the MEP/M wave amplitude ratio, the central motor conduction time (CMCT), the SP threshold, the interthreshold difference (ITD), and the SP duration (SPD). RESULTS: The main finding was an increase in the ITD in patients with mild and moderate head injury due to the relatively greater augmentation of the MEP threshold. This was associated with a reduction of the MEP/M wave amplitude ratio. The degree of MEP and SP changes depended on severity of head injury and was not related to the type of brain lesions. The SPD did not differ significantly in brain concussion, or diffuse, focal and combined brain injury groups compared with the control group. The CMCT was prolonged in patients with diffuse and combined brain lesions. Among subjective complaints only fatigue was significantly related to ITD, MEP, and SP threshold abnormalities. CONCLUSIONS: The results suggest that mechanisms involved in MEP and SP generation are differently affected in head injury, the first being impaired more severely. The increase of the ITD accompanied by reduction of the MEP/M wave amplitude ratio may reflect a dissociated impairment of inhibitory and excitatory components of central motor control in head trauma.

Hemodynamic consequences of cerebral vasospasm on perforating arteries: a phantom model study.

BACKGROUND AND PURPOSE: Hemodynamics of cerebral vasospasm after subarachnoid hemorrhage remain unclear, and the discrepancy between ultrasonographic or angiographic evidence of arterial narrowing and neurological ischemic deficit is still debated. Most blood flow studies have been involved with large arteries, and thus, very little is known regarding the hemodynamic behavior of small perforating vessels. Patients with symptomatic vasospasm, however, often present with neurological signs suggesting involvement of deep-sited areas of the brain supplied by perforating arteries. METHODS: A pulsatile pump was set to provide an outflow of 350 mL/min through a 10-mm-diameter C-flex tube at a perfusion pressure of 130/80 mm Hg. The perfusion fluid used was prepared to approximate blood viscosity. Perforating arteries were simulated by a 1-mm tube connected to the parent tube at a 90 degrees angle. Cylindrical stenotic devices of decreasing diameters were then introduced into the parent tube at the level of the aperture of the secondary tube and 1.5 diameters upstream of it. Velocity profiles both proximal and distal to the stenosis in the parent tube were obtained with a newly developed ultrasonographic flowmeter that allows for high spatial resolution. RESULTS: Increasing stenosis resulted in decreased outflow in the main tube, although it was significant only with severe stenosis. Whenever the simulated stenosis was placed upstream of the secondary tube, flow reduction was associated with a progressive change in the velocity profile, which gradually changed from laminar conditions to a jet stream limited to the center of the lumen. Further diameter reduction was responsible for the occurrence of flow separation with retrograde flow velocities in the periphery of the lumen. In the secondary tube, flow reduction was much more pronounced and began at a lesser degree of stenosis. Increasing fluid viscosity and decreasing perfusion pressure enhanced flow separation and prominently affected the outflow in the secondary tube. Conversely, whenever the simulated stenosis involved the branching area of the secondary tube, there was a slightly progressive decrease in the relative flow in the main tube as the stenosis became tighter. When the stenosis equaled the diameter of the secondary tube, the relative contribution of the secondary tube increased markedly at the expense of the main tube outflow. CONCLUSIONS: The present results show that local cerebral vasospasm induces changes in postvasospastic velocity profile affecting the shear rate and may eventually lead to flow separation. This phenomenon may, in turn, result in a venturi-like effect over the aperture of perforating arteries branching out of the postvasospastic portion of the affected parent artery. These alterations of cerebral hemodynamics may account for at least part of the vasospasm symptomatology, especially in the vertebrobasilar system, where vasospasm is commonly focal rather than diffuse. Furthermore, these changes proved to be affected significantly by manipulations of pressure and viscosity, supporting the use of hyperdynamic therapy in the management of cerebral vasospasm.

Results of otovestibular tests in mild head injuries.

The neurotological workup of patients with minor head trauma was carried out prospectively. The preliminary results of the ongoing study were derived from 38 subjects (12 female, 26 male) at an average age of 33.5 years. All had been hospitalized after having suffered minimum head trauma followed by a temporary loss of consciousness, by amnesia, or by vomitting. The 38 subjects underwent the examination within 72 hours of the event and were summoned for a follow-up visit 3 months later. The anamnestic data show that the most frequent complaint was dizziness (81%). Tinnitus was noted in fewer than one-half of the patients, with a variety of descriptions. Twenty-six percent complained of hearing loss. The correlation between reported hearing loss and the finding on subsequent behavioral audiometry (within 72 hours after the event) was studied. The sensitivity of hearing loss (as complaint) was found to be only 40%, but its specificity was much higher at 83%. The overall equilibrium reflected in the composite score of the sensory testing in computed dynamic posturography actually worsened between tests. A good correlation was found between posturography results and symptomatology. We concluded that, after minor head trauma, most patients suffer from dizziness, and more than one-half complain of tinnitus or hearing loss. The unsteadiness does not subside within 3 months after concussion. A more protracted follow-up is required to summarize the outcome of head injury from a neurootological point of view. A clear correlation is found between complaints and posturography results. After minor head trauma, pure vestibular injuries are much less frequent than are central lesions. Motor dysfunction is less frequent than are the sensory abnormalities.

Brain natriuretic peptide and cerebral vasospasm in subarachnoid hemorrhage. Clinical and TCD correlations.

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.

Penetrating head injuries caused by a new weapon, the side dome.

The "side dome" is a mix of high and low explosives with a multitude of small metal balls molded within a specially designed half-sphere that directs the explosion wave and the projectiles in one direction to augment the harm. This weapon, originally designed by guerrilla and terrorist groups, is now used by regular armies. This report presents one craniocervical and eight cranial injuries caused by this new weapon and discusses the cases' various clinical features, the paucity of intracerebral cavitation damage along the missile track, the need for only minimally aggressive surgery, and the relatively favorable outcome. In all cases, the helmet offered good protection and the entry of the projectiles was just below its rim in an upward direction.

Dissociation of somatosensory and motor evoked potentials in non-comatose patients after head injury.

OBJECTIVES: This study was performed to evaluate the clinical value of combined use of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) in patients with different brain lesions after head trauma. METHODS: A total of 64 patients with minor and moderate head injury were investigated by means of SEPs recorded over the parietal and frontal areas and MEPs following single-pulse transcranial magnetic stimulation (sTMS) and slow-rate repetitive transcranial magnetic stimulation (rTMS). RESULTS: In almost 50% of the patients, a dissociated impairment of somatosensory and motor evoked potentials was found. This dissociation was related to different distribution of SEP and MEP abnormalities in head injury subgroups. The higher threshold to sTMS and increased variability of the MEP amplitude during slow-rate rTMS were the most prominent features in patients with focal brain contusions, suggesting impairment of the cortical excitability. SEP abnormalities, as well as central conduction impairments, were more noticeable in patients with diffuse brain injury. CONCLUSIONS: A combined analysis of SEPs and MEPs may improve the assessment of cortical dysfunctions and central conduction abnormalities in non-comatose patients with head injury. A slow-rate rTMS may be considered as a complementary technique to the evaluation of the threshold in assessment of the excitability of the motor cortex in minor and moderate head injury.

[Exhaustion of motor cortex after head injury--revealed by transcranial magnetic stimulation].

We evaluated the pattern of motor evoked potentials elicited by single-pulse and slow-rate (1 Hz) repetitive, transcranial, magnetic stimulation (RTMS) in minor head injuries. The motor response to a single magnetic stimulus in patients with minor head injury was characterized by a significantly higher threshold than in healthy subjects. However, central and peripheral motor conduction was normal in all patients. A stable pattern of MEP throughout the RTMS session was the most prominent feature in the control group. A progressive decrease in MEP amplitude and irregular alternation of large and very small MEPs over the course of RTMS was observed in minor head injury. The higher threshold of the motor response and the abnormal patterns of MEP behavior revealed by RTMS may reflect impaired excitability and enhanced exhaustion of the motor cortex in patients with minor head injuries, which improve with time.

Altered excitability of the motor cortex after minor head injury revealed by transcranial magnetic stimulation.

This study attempts to find out whether the motor evoked potential (MEP) elicited by single pulse and slow-rate (1 Hz) repetitive transcranial magnetic stimulation (TMS) can disclose concealed subclinical impairments in the cerebral motor system of patients with minor head injury. The motor response to single pulse TMS (STMS) of the patient group was characterized by significantly higher threshold compared with that of the control group. The central motor conduction time, as well as the peripheral conduction time were normal in all patients pointing to cortical impairment. Two main patterns of MEP changes in response to repetitive TMS (RTMS) were observed in the patient group. A.--progressive decrease of the MEP amplitude throughout the stimulation session to a near complete abolition. B.--irregularity of the amplitude and the waveform of the MEP in a chaotic form. The MEP latency remained stable during the whole stimulation session. The MEP abnormalities recovered gradually over the period of a few months. The higher threshold of the motor response to STMS and the abnormal patterns of the MEP to RTMS seem to reflect transient impairment of cortical excitability or "cortical fatigue" in patients who sustained minor head injures. Further study is needed to evaluated the extent and the pathophysiological mechanisms of the central nervous system fatigue phenomenon following head injury.