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beta -amyloid precursor protein positive axonal bulbs may form in non-head-injured patients.

Since the early 1980s axonal bulbs staining positively for beta-amyloid precursor protein (betaAPP) have been used as a marker of diffuse axonal injury (DAI), bulb formation been attributed to shearing forces generated during rotational acceleration/deceleration head injury. This study draws attention to the observation that they may form in the absence of a head injury and, thus, axonal injury cannot be assumed to result from mechanical injury alone. Out of 20 cases with no history of head injury studied, which only showed evidence of neuronal hypoxic change, 11 (55%) showed variable positive staining for betaAPP in a similar anatomical distribution to that previously described for DAI. The role of hypoxia in the formation of axonal bulbs, as well as the possible role of betaAPP as an acute phase protein, are discussed. These observations further clarify the pattern and relationship between neuronal and axonal staining observed following a brain insult and emphasize the possible role of betaAPP as a neuroprotective protein.

Journal Article↗

Modulation of stretch-induced enhancement of neuronal NMDA receptor current by mGluR1 depends upon presence of glia.

Stretching of cultured neurons has been used to model diffuse axonal injury associated with brain trauma. N-Methyl-D-aspartate receptor (NMDAR) activation and group I metabotropic glutamate receptors (mGluRs) are implicated in the pathophysiology of such injury. Here we detail the effects of culture condition and mGluR1 modulation on stretch-enhanced NMDA receptor activity, and show the presence of mGluR1 in addition to mGluR5 in glia. In cortical neurons grown in the absence (PN) or presence (NG) of a glial monolayer, stretch injury (5.7 mm) enhances NMDAR activity by increasing maximal NMDAR current, decreasing the voltage-dependent Mg(2+) block, and altering the kinetic behavior of these receptors. In PN cultures, activation of mGluR1 increases stretch-enhanced NMDAR activity, whereas in NG cultures, such activity is reduced. In contrast, inhibition of mGluR1 in PN cultures limits stretch-enhanced NMDAR activity, whereas in NG cultures activity is increased. MGluR1 modulate stretch-enhanced NMDAR activity through multiple mechanisms including: altering peak or steady state current, affecting Mg(2+) blockade of the NMDAR, or by changing NMDAR kinetics. The presence of glia significantly alters the nature of mGluR1-mediated modulation of NMDAR activity and stretch-induced injury. Together these data indicate a significant neuronal/glial interaction between glial mGluR1 and neuronal NMDA receptor activity.

Animals↗

Pathophysiological changes of the central auditory pathway after blunt trauma of the head.

It is the aim of the present paper to correlate clinical symptoms of auditory dysfunction (tinnitus, hyperacusis, hearing loss) one year on average after a blunt trauma of the head with objective audiological test results (otoacoustic emission and auditory brainstem response testing, impedance audiometry) and to compare these findings to controls without history of head trauma. Thirty-one patients (24-56 years) were included. They were largely female (n = 26). The clinical and otolaryngological examination (including otoscopy) of all patients revealed no pathological abnormalities. Pure-tone audiograms were normal with one exception (pre-existing noise-induced hearing loss) as well as tympanograms. The main auditory symptoms were tinnitus (n = 9), hyperacusis (n = 2) and a reported transient hearing loss immediately after the trauma (n = 16) (which had improved at the time of examination). The results of testing the central auditory pathway showed that the transiently evoked otoacoustic emissions (otoemissions) revealed statistically significant differences between amplitude differences of all patients as well as patients with tinnitus and controls in the linear, but not in the non-linear stimulation mode. A complete loss of stapedial reflex responses was found in 12 of the patients and a partial (irregular) loss (in at least more than two frequencies) in four additional patients. Auditory brainstem responses (ABR) were normal in all patients, but 76% had lowered loudness discomfort levels (LDL). Blunt trauma of the head can lead to auditory dyfunction, probably as a result of diffuse axonal injury of the central auditory pathway. An initial sensorineural hearing loss after the trauma (as a result of the inner ear fluid concussion) was transiently reported only. Auditory symptoms play a minor role in the so-called "postconcussive syndrome," but should be considered and evaluated fully.

Adult↗

Rapid spontaneous disappearance of an acute extradural hematoma: case report.

The authors report the case of a patient presenting with an acute extradural hematoma and diffuse axonal injury. Control CT scan performed 4 hours later showed the complete resolution of the extradural collection together with increased evidence of shearing injuries. The mechanism of the hematoma resolution may probably be related to the concomitant acute brain swelling.

Accidents, Traffic↗

Traumatic basal ganglia hemorrhage: clinicopathologic features and outcome.

Traumatic basal ganglia hemorrhage (TBGH) is probably secondary to rupture of lenticulostriate or anterior choroidal arteries. We evaluated 6 consecutive cases of this entity to define its clinical and pathologic dimensions. Relative frequency of TBGH was 3% (3 left, 3 right) in this acute rehabilitation population. Lesion size and associated pathology varied. Contralateral hemiparesis, present in all, recovered to varying extents, apparently related to lesion location (posterior limb, internal capsule, or midperiventricular white matter), not size. Prolonged muteness occurred in 4 of 6; these 4 patients also had severe diffuse axonal injury. Clinical findings corresponded with previously recognized subcortical hemisphere profiles. All achieved a moderate disability or good recovery rating on the Glasgow Outcome Scale. Rather than any features of the TBGH itself, duration of coma and/or associated temporal herniation predicted slower recovery and worse outcome. In conclusion, TBGH is a rare entity compatible with a favorable recovery, especially when occurring in isolation. The hemorrhage itself determines clinical signs related to particular subcortical structures involved and the side of the lesion. Overall cognitive impairment and speed and quality of recovery are more related to associated cerebral damage.

Adolescent↗

Traumatic atlanto-occipital dislocation: presentation of a new posterior occipitoatlantoaxial fixation technique in an adult survivor: technical case report.

OBJECTIVE AND IMPORTANCE: More survivors of traumatic atlanto-occipital dislocation (AOD) in adults have recently been reported. Surgical management options are therefore of increasing interest. We present a new technique of posterior C0-C1-C2 fixation. CLINICAL PRESENTATION: A 29-year-old motorcyclist survived a traumatic vertical AOD of 15 mm. No spinal cord or medullary lesion was present. Brain contusion and diffuse axonal injuries led to a cortical biplegia, which recovered progressively over a period of 6 months. Twelve months after surgery, no neurological deficit was present except for slightly increased deep tendon reflexes. INTERVENTION: Posterior C0-C1-C2 fixation was performed with two bicortical occipital screws, one bicortical lateral mass screw in the atlas, and one monocortical pars screw in the axis on each side, connected to a plate-rod on the right and left sides. Fusion was performed with monocortical bone graft from the posterior iliac crest. CONCLUSION: The surgical technique described was thought to be safe to perform and resulted in immediate stability without external immobilization. Solid fusion was achieved 6 months after surgery.

Adult↗

[Cerebral contusion in victims of fatal traffic accidents. Frequency and association with other craniocerebral lesions].

A morphological study, macro and microscopical, was made of brain lesions in 120 victims of fatal road traffic accidents. Contusions of the brain were identified in 67 (55.8%) of the patients. The contusions especially affected the orbital surfaces of the frontal lobes (27.8%) and the temporal poles (19.8%). The recent brain contusion was associated with a skull fracture in 70.1% of the cases and with a diffuse axonal injury in 89.5%. These can be explained by the association of contact and inertia from the road traffic accidents. Old contusions were identified in six patients (5.0%).

Accidents, Traffic↗

Cervical epidural haematoma with clivus fracture: case report.

Clivus fractures are rare and severe entities, usually associated with vascular or cranial nerve lesions and frequently diagnosed postmortem. Cervical epidural haematomas can be traumatic or spontaneous, manifested in acute or chronic form, and are treated surgically in the majority of cases, although the conservative treatment also can be indicated to patients with incomplete and non-progressive deficits. The authors report the case of a female patient, 8 years old, victim of trampling in public way by a high velocity motorized vehicle, admitted in Glasgow 7, anisocoric pupils (left pupil midriatic), whose radiological investigation showed a transverse fracture of the clivus, cervical epidural haematoma and diffuse axonal injury. The patient was submitted to intracranial pressure monitorization, sedation and conservative treatment with dexamethasone, with good outcome. The authors also present a literature review.

Accidents, Traffic↗

Clinical significance of traumatic subarachnoid hemorrhage.

The clinical significance of traumatic subarachnoid hemorrhage (TSAH) was studied in 20 head-injured patients. They were classified into mild (9) and severe (11) groups by their initial Glasgow Coma Scale (GCS) scores. TSAH detected by computed tomography was localized in the Sylvian fissure in four of the nine mild group patients, but was also found in other basal subarachnoid cisterns in the other five. Except for one patient who developed delayed vasospasm and communicating hydrocephalus, all had favorable outcomes in this group. Massive TSAH was noted in the basal subarachnoid cisterns in 10 severe group patients and only one had a good outcome. Delayed intracerebral hematoma in the frontal or temporal lobe in the vicinity of the Sylvian fissure was found in two mild and two severe group patients with TSAH in the Sylvian fissures. Traumatic parenchymal lesions in the brainstem were minimal in one of the two autopsied patients and no evidence of diffuse axonal injury was found in both cases. Thus, TSAH in the Sylvian fissure is suggestive of focal brain contusion around the fissures. Massive TSAH in the basal subarachnoid cisterns is not necessarily associated with severe parenchymal injury of the brainstem.

Adolescent↗

[Diffuse axonal lesions in childhood].

OBJECTIVE: About 48% of all primary traumatic intracranial lesions are represented by so-called Diffuse Axonal Injury (DAI): a pathologic condition characterized by multiple microscopic lesions and hemorrhage at the level of midline cerebral structures, in the subcortical grey matter, and/or within the brainstem. The natural history of DAI is depressing: 100% of the patients deteriorate rapidly to coma and approximately 50% die, while 50% remain in a vegetative state or with severe neurological deficits. In the present report, we describe the results of a study aimed to evaluating the cerebral hemodynamics and the neuroradiological findings observed in four children (6, 8, 10 and 12 years old) affected by DAI. METHODS: All the patients had been admitted to the Pediatric Intensive Care Unit with Glasgow Coma Score (GCS) of 5. On admission, all patients underwent mechanical ventilation, antiedemigen and barbiturates therapy. Serial CT scan and Transcranial Doppler Sonography (TCD) examinations were carried out in all children. TCD of the middle cerebral arteries was performed through the temporal window. The children underwent insertion of a ventricular catheter for intracranial pressure monitoring. Follow-up time has been, respectively, 4 years, 3 years, 7 and 1 months. RESULTS: The Glasgow Outcome Score (GOS) of three children is 2 (persistent vegetative state), while the GOS of the one child is 3 (severe neurological deficits). CONCLUSION: DAI results in unfortunate prognosis and large health care costs. The proper medical management of this condition should be based on TCD and SjO2 and CEO2 evaluations, in order to monitor efficaciously the cerebral blood flow.

Adolescent↗

Restoration of vision IV: role of compensatory soma swelling of surviving retinal ganglion cells in recovery of vision after optic nerve crush.

PURPOSE: Diffuse axonal injury following partial optic nerve crush (ONC) leads to severe visual deficits from which rats can partially recover within 2-3 weeks. To evaluate tbc role of surviving retinal ganglion cells (RGCS) in recovery, we have observed their morphology repeatedly in vivo with ICON-microscopy and correlated cell size changes with recovery of vision which we observed in parallel in the same animals. METHODS: After rats had learned a visual contrast discrimination task using an automated, computer-based test, RGCs were labeled retrogradely with fluorescent beads. Animals then received either no lesion, a complete axotomy or bilateral mild, moderate or severe ONC. Before surgery and for 40 days post-operatively, ROC number and soma size was repeatedly quantified every five days with tbc in vivo confocal neuroimaging method (Sabel et al., Nature med. 3, 1997, p. 244). In parallel, visual function was quantified with the contrast-discrimination task. RESULTS: After ONC about 70 % of the ROCs died after having undergone a fast and massive soma swelling. The extent of cell death was independent of crush severity. RGCs surviving the injury did not change their body size over time in the severe group and these animals also did not recover their vision. In contrast, after a mild or moderate crush, about half of the surviving RGCs experienced a slow and moderate, "compensatory" cell soma swelling and the rats showed partial recovery of vision. Both the number of RGCs showing such compensatory soma swelling and the extent of the swelling correlated highly (r = 0.96) with recovery of contrast discrimination performance at post-operative days 23 and 38. CONCLUSIONS: Depending en the time course and extent, soma swelling after neurotrauma may be associated either with cell death or recovery of function. Because of the very high correlation between extent of recovery and amount of soma swelling, moderate soma swelling contributes in a prominent way to recovery of vision. We believe that these cells provide an important structural substrate for neuronal tissue repair and therefore term these cells "compensatory neurons".

Adaptation, Physiological↗

[Epidemiology of head traumas. "Barcelona" data base. Objectives, design and analysis of 584 cases].

INTRODUCTION: Descriptive analysis of some features in patients with cranio-encephalic traumatisms (CET) admitted to our hospital and collected in a data base, in order to establish the prognosis of the lesions and apply the most appropriate diagnostic and therapeutic procedures. MATERIAL AND METHODS: Since July 1987 to June 1989 we collected data on 584 patients with CET who presented the following selection criteria: consciousness level lower than 13 points in the Glasgow scale and/or pathologic computerized tomography. According to the consciousness level (Glasgow scale) on admission, patients were classified into three groups: slight CET (Glasgow 15-13), moderate CET (Glasgow 12-9), and severe CET (Glasgow < 9). The traumatic mechanisms were divided into 8 categories (occupant, pedestrian, motorbike, aggression, labor, drop, sporting, cyclist). According to the main lesion we considered the following diagnoses: subdural hematoma, epidural hematoma, cerebral contusion (s), diffuse lesion with normal computerized tomography and/or subarachnoid hemorrhage, cerebral congestion, and diffuse axonal lesion. Results were evaluated six months after using the Glasgow scale. RESULTS: The mean age of patients with slight CET was 37.7 +/- 22.1 years, those with moderate CET 31.7 +/- 22.6 years, and those with severe CET 30.8 +/- 21.6 years. Four hundred and forty-two were men (75.6%). The time period between the accident and hospital admission could be determined in 512 cases (87.6%). Severe CET arrived to the hospital (4.8 +/- 7.3 hours) earlier than the other groups (6.6 +/- 11.9 hours in moderate CET and 14.2 +/- 23 hours in slight CET). Most of patients, 488 (83.5%), were referred from another hospital, whereas the remaining cases came directly from the accident place. Traumatic mechanisms according to the previous categories were: occupant 145 (25%), pedestrian 112 (20%), motorbike 104 (18%), cyclist 2 (0.003%), labor 39 (7%), drop 154 (27%), sporting 7 (1%), aggression 10 (2%). Percentage of traffic accident was higher in patients with severe CET (74.6, 64, and 47% in severe moderate, and slight CET, respectively). The main lesions were: acute subdural hematoma, 72 (12.3%); cerebral contusion, 207 (35.4%); epidural hematoma, 88 (15%); normal computerized tomography/subarachnoid hemorrhage, 87 (14.8%); swelling, 17 (2.9%); diffuse axonal injury, 74 (12.6%); and the remaining, 39 (6.6%) had other lesions such as hydrocephalus fracture-sinking, etc. Mortality was 44.2, 12.2, and 3.7% respectively in severe, moderate, and slight CET. CONCLUSIONS: Data base may contribute to establish the prognosis of CET and to determine the efficacy of therapeutic procedures as well as that of diagnostic and investigational methods.

Adolescent↗

[Prolonged traumatic coma caused by diffuse axonal lesions].

A 22-year old male patient was admitted for deep coma probably of traumatic origin. There was neither fracture of the skull nor expansive intracranial lesion. The patient survived for 6 years and 8 months without any change in consciousness. Post-mortem neuropathological examination showed lesions which predominated in the white matter and had features that were compatible with diffuse axonal injury. The mechanism responsible for these lesions seems to be stretching and shearing of axones at the moment of impact. The exceptionally long duration of survival probably accounts for the severity of the lesions observed.

Adult↗

Lesion of dentatothalamic pathways in severe post-traumatic tremor.

The present study investigates evidence of dentatothalamic pathway lesions in nineteen patients with severe kinetic post-traumatic tremor respectively by magnetic resonance imaging (MRI). Kinetic tremor is thought to be characteristic of lesions of the cerebellar outflow. While this hypothesis is supported by experimental data, neuropathological and neuroradiological findings have been limited. The appendicular tremors were unilateral in 13 patients and bilateral in 6, accounting for 25 instances of tremor. The tremor developed after severe head trauma in 18 patients. These patients had evidence of diffuse axonal injury on MRI. Postural and kinetic tremor was present in all patients, and was accompanied by tremor also present at rest in 14 instances. Multiplanar MRI studies were performed on a high-field MRI system operating at 2.0 T in 13 patients and on intermediate-field strength MRI systems in 6 patients according to a standardized protocol. To detect small deposits of hemosiderin after post-traumatic lesions, the protocol included a heavily T2-weighted spin-echo pulse sequence. Lesions of the dentatothalamic pathways were found in 22 instances. The lesions were classified into different types of according to their distribution. A lesion of the dentate nucleus ipsilateral to the tremor (type 1) was found in one instance (4%), lesions involving the ipsilateral predecussational dentatothalamic pathway (type II and III) were found in 14 instances (56%), and lesions involving the contralateral post-decussational course (type IV) in 7 instances (28%). One patient with a mild head trauma had a lesion of the contralateral thalamus. The lesions appeared as hypointense, hyperintense or mixed. Two of three patients with a parkinsonian-like rest tremor had type IV lesions involving the substantia nigra. The nosological concepts of tremors are discussed. 'Midbrain' tremor may have distinct pathoanatomical lesion sites.

Adult↗