Multimodal assessment of recovery from coma in a rat model of diffuse brainstem tegmentum injury.

Despite the association between brainstem lesions and coma, a mechanistic understanding of coma pathogenesis and recovery is lacking. We developed a coma model in the rat mimicking human brainstem coma, which allowed multimodal analysis of a brainstem tegmentum lesion's effects on behavior, cortical electrophysiology, and global brain functional connectivity. After coma induction, we observed a transient period (∼1h) of unresponsiveness accompanied by cortical burst-suppression. Comatose rats then gradually regained behavioral responsiveness concurrent with emergence of delta/theta-predominant cortical rhythms in primary somatosensory cortex. During the acute stage of coma recovery (∼1-8h), longitudinal resting-state functional MRI revealed an increase in functional connectivity between subcortical arousal nuclei in the thalamus, basal forebrain, and basal ganglia and cortical regions implicated in awareness. This rat coma model provides an experimental platform to systematically study network-based mechanisms of coma pathogenesis and recovery, as well as to test targeted therapies aimed at promoting recovery of consciousness after coma.

[Functional effects of transcranial electromagnetic stimulation (60 and 70 Hz) of the brain of intact rats and rats with acute brainstem damage].

Behavior and brain electrical activity of 79 male Wistar rats (intact and with acute experimental brainstem injury) were studied during the course of therapeutic transcranial electromagnetic stimulation (TEMS) with frequencies 60 and 70 Hz. In intact animals this effect was accompanied by a decrease in voluntary motor activity and increase in synchronization of the brain electrical activity, in particular, in the delta and beta1 frequency ranges. This inhibitory effect was similar to that of sleep. In the early period of acute experimental stem pathology, the TEMS course was accompanied by suppression of EEG signs of adaptive post-operative stress response and could lead to increased severity of the condition of an animal, along with the slowing of postoperative recovery. Cytomorphological evidence was obtained to the importance of vascular factor in the formation of cerebral reactions to TEMS.

Paresia de III par craneal y afectación troncoencefálica por difusión intradural de anestesia retrobulbar / III cranial nerve palsy and brainstem disfunction following retrobulbar anaesthesia

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[Rehabilitation of children after craniocerebral injuries with particular attention paid to the reflex stimulation Powiertowski's method. Preliminary study]. / Usprawnianie dzieci po przebytych urazach czaszkowo-mózgowych ze szczególnym uwzglednieniem metody stymulacji odruchowej Hieronima Powiertowskiego. Doniesienie wstepne.

INTRODUCTION: An increasing number of craniocerebral injuries among children is becoming a serious therapeutic problem for emergency wards and for chronic treatment wards. The most important problem among these patients is a lengthening period of consciousness disorders. The aim of the study is to present a sample method of rehabilitation of children with brain injury. MATERIAL AND METHODS: The rehabilitation process comprised 15 children with brain injury, including 8 with cerebral hemisphere injury and 7 with brain stem injury. The method of early motion rehabilitation was applied. It was developed by H. Powiertowski in 1970's. In the years 1991-1999 the method was used at the Children's Ward of the Department of Rehabilitation by Professor Krystyna Dobosiewicz. RESULTS: As a result of the applied method, 13 out of 15 children with brain injuries regained consciousness. 2 girls with severe lesion of the brain, still unconscious were transferred to the intensive care ward in the place of residence. CONCLUSIONS: Powiertowski's method of motion stimulation, which is presented in this paper, turned out to be successful in the process of rehabilitation children with brain injury treated in the Department of Rehabilitation.

Pathology of post traumatic brainstem and hypothalamic injuries.

OBJECTIVE: Several autopsy studies of head injury are available but pathology of brainstem and hypothalamic injuries are addressed in very few of them. We studied brains of 47 patients who succumbed to head injury, with special attention to topographical distribution of brainstem and hypothalamic injuries. MATERIAL AND METHODS: Brains retrieved at autopsy of 47 patients who succumbed to head injury following road traffic accidents (32 cases) or fall from height (15 cases) were examined for brainstem and hypothalamic injuries. Brainstem lesions were grouped into Type I (in absence of raised intracranial pressure and downward herniation) and Type II (secondary to raised ICP and herniation). Lesions were mapped topographically and examined histologically for axonal and myelin changes. Anatomical location of lesions was correlated with mode of injury, site of impact, occurrence of associated lesions, prognosis and survival. RESULTS: Brain-stem injury was noted in 36 cases (76.5%) [Type I in 7 (14.9%) and Type II in 29 cases (61.7%)]; hypothalamic injuries in 20 (42.5%), and combined hypothalamic and brainstem injuries were seen in 17 (36.1%). 11 had no brainstem/hypothalamic injuries. Brainstem hemorrhages occurred in lower midbrain and upper pons, and hypothalamic injuries involved paraventricular nuclei. In cases with combined injury to brainstem and hypothalamus, lesions involved rostral ventral mesencephalon of brainstem and paraventricular region of hypothalamus. The site of impact had no definite correlation with occurrence of brainstem or hypothalamic injuries though basal fractures and road traffic accidents were more often associated with hypothalamic injuries. Survival of cases with Type I injury was shorter than Type II (14.2 vs. 65.2 hours) due to involvement of raphe/reticular nuclei. Though cases with hypothalamic injuries did not result in early death, involvement of anterior hypothalamus resulted in shorter survival (< 6 hours) compared to posterior. Diffuse axonal injury and hypothalamic involvement were more often seen with Type II brainstem injuries. Cerebral contusions were a common accompaniment of hypothalamic injuries (80%). CONCLUSIONS: Brainstem and hypothalamic injuries are seen in significant proportion of traumatic brain injuries and may have an important role in determining the survival and prognosis. Insight into mechanisms of injury to hypothalamo-brainstem axis is essential for evolving better therapeutic strategies and prevention of post traumatic long term sequelae.

Motor cortex stimulation in patients with deafferentation pain: activation of the posterior insula and thalamus.

OBJECT: The mechanisms underlying deafferentation pain are not well understood. Motor cortex stimulation (MCS) is useful in the treatment of this kind of chronic pain, but the detailed mechanisms underlying its effects are unknown. METHODS: Six patients with intractable deafferentation pain in the left hand were included in this study. All were righthanded and had a subdural electrode placed over the right precentral gyrus. The pain was associated with brainstem injury in one patient, cervical spine injury in one patient, thalamic hemorrhage in one patient, and brachial plexus avulsion in three patients. Treatment with MCS reduced pain; visual analog scale (VAS) values for pain were 82 +/- 20 before MCS and 39 +/- 20 after MCS (mean +/- standard error). Regional cerebral blood flow (rCBF) was measured by positron emission tomography with H2(15)O before and after MCS. The obtained images were analyzed with statistical parametric mapping software (SPM99). RESULTS: Significant rCBF increases were identified after MCS in the left posterior thalamus and left insula. In the early post-MCS phase, the left posterior insula and right orbitofrontal cortex showed significant rCBF increases, and the right precentral gyrus showed an rCBF decrease. In the late post-MCS phase, a significant rCBF increase was detected in the left caudal part of the anterior cingulate cortex (ACC). CONCLUSIONS: These results suggest that MCS modulates the pathways from the posterior insula and orbitofrontal cortex to the posterior thalamus to upregulate the pain threshold and pathways from the posterior insula to the caudal ACC to control emotional perception. This modulation results in decreased VAS scores for deafferentation pain.

MRI patterns in prolonged low response states following traumatic brain injury in children and adolescents.

OBJECTIVES: To explore the relationship between location and pattern of brain injury identified on MRI and prolonged low response state in children post-traumatic brain injury (TBI). METHODS: This observational study compared 15 children who spontaneously recovered within 30 days post-TBI to 17 who remained in a prolonged low response state. RESULTS: 92.9% of children with brain stem injury were in the low response group. The predicted probability was 0.81 for brain stem injury alone, increasing to 0.95 with a regional pattern of injury to the brain stem, basal ganglia, and thalamus. CONCLUSIONS: Low response state in children post-TBI is strongly correlated with two distinctive regions of injury: the brain stem alone, and an injury pattern to the brain stem, basal ganglia, and thalamus. This study demonstrates the need for large-scale clinical studies using MRI as a tool for outcome assessment in children and adolescents following severe TBI.

Hypothalamus-brain stem circuitry responsible for vagal efferent signaling to the pancreas evoked by hypoglycemia in rat.

Circulating glucose levels significantly affect vagal neural activity, which is important in the regulation of pancreatic functions. Little is known about the mechanisms involved. This study investigates the neural pathways responsible for hypoglycemia-induced vagal efferent signaling to the pancreas and identifies the neurotransmitters involved. Vagal pancreatic efferent nerve activities were recorded in anesthetized rats. Insulin-induced hypoglycemia, a decrease of blood glucose levels from 114 +/- 5 to 74 +/- 6 mg dl(-1), stimulated an increase in pancreatic efferent nerve firing from a basal rate of 1.1 +/- 0.3 to 19 +/- 3 impulses 30 s(-1). In contrast, vagal primary afferent neuronal discharges recorded in the nodose ganglia were unaltered by systemic hypoglycemia. Vagal afferent rootlet section plus splanchnicotomy had no effect on hypoglycemia-induced vagal efferent firing, suggesting a central site of action. Decerebration reduced the increase in nerve firing stimulated by hypoglycemia from 21 +/- 4 to 9.6 +/- 2 impulses 30 s(-1). Chemical ablation of the lateral hypothalamic area, but not the arcuate nucleus, inhibited pancreatic nerve firing evoked by hypoglycemia. Microinjection of the orexin-A receptor antagonist SB-334867 into the dorsal motor nucleus of the vagus (DMV) inhibited pancreatic nerve firing evoked by insulin-induced hypoglycemia by 56%. In contrast, injection of orexin-A (20 pmol) into the DMV elicited a 30-fold increase in pancreatic nerve firing. We concluded that systemic hypoglycemia stimulates pancreatic efferent nerve firing through a central mechanism. Full expression of pancreatic nerve activities during hypoglycemia requires both the forebrain and the brain stem. In addition to activating neurons in the brain stem, central neuroglucopenia activates subpopulations of neurons in the lateral hypothalamic area that contain orexin. The released orexin acts on DMV neurons to stimulate pancreatic efferent nerve activities and thus regulate pancreatic functions.

[Comparison and examination of stereotactic surgical complications in movement disorders].

The purpose of the present study was to determine exactly the incidence of surgical complications in patients for whom MRI-targeted, microelectrode recording (MER)-guided implantation of deep brain stimulation (DBS) or radiofrequency (RF)-coagulation surgery was performed. Between January, 1998 and September, 2002, a total of 110 stereotactic surgeries for movement disorders (57 RF-coagulations and 53 implantations of DBS) were performed. We investigated the type and number of complications for each of the following surgical targets; globus pallidus, thalamus, and subthalamic nucleus (STN). Twenty-four neurological complications in 22 patients and 16 radiological/instrumental complications in 16 patients were verified among the 110 surgeries. Among the neurological complications, hemiparesis and mental disturbances were observed at a high rate, while intraoperative hemorrhage frequently occurred among the radiological/instrumental complications. The rate of neurological and radiological/instrumental complications for each of the stereotactic targets; the globus pallidus, thalamus, and STN-targeted surgeries, was 32.4%, 16.7%, 18.8% and 16.2%, 20.0%, 12.5%, respectively. The reason for the high rate of intraoperative hemorrhage may be associated with technical problems resulting from the penetration of vessels by needles, as well as the destruction of small vessels due to heat ablation. As for the mental disturbances, visual hallucinations (VH) occurred a high rate, especially during STN-DBS. Peduncular damage and/or L-dopa toxicity due to STN-DBS may have been associated with VH, so the STN-DBS may therefore be thought to change the threshold of stimulus-induced hallucinations. We also found that the procedures for DBS surgery, especially in younger patients, have a lower risk of complication, while, on the other hand, coagulation surgery for elderly patients is accompanied by of high risks, from the standpoint of surgical complications.

DBS and diathermy interaction induces severe CNS damage.

Pulse-modulated radiofrequency diathermy treatment to the maxilla produced permanent diencephalic and brainstem lesions and a vegetative state in a patient with PD with implanted subthalamic electrodes for deep brain stimulation.

Air-puff-induced facilitation of motor cortical excitability studied in patients with discrete brain lesions.

Air-puff stimulation applied to a fingertip is known to exert a location-specific facilitatory effect on the size of the motor evoked potentials elicited in hand muscles by transcranial magnetic stimulation. In order to clarify its nature and the pathway responsible for its generation, we studied 27 patients with discrete lesions in the brain (16, 9 and 2 patients with lesions in the cerebral cortex, thalamus and brainstem, respectively). Facilitation was absent in patients with lesions affecting the primary sensorimotor area, whereas it was preserved in patients with cortical lesions that spared this area. Facilitation was abolished with thalamic lesions that totally destroyed the nucleus ventralis posterolateralis (VPL), but was preserved with lesions that at least partly spared it. Lesions of the spinothalamic tract did not impair facilitation. The size of the N20-P25 component of the somatosensory evoked potential showed a mild correlation with the amount of facilitation. The facilitation is mainly mediated by sensory inputs that ascend the dorsal column and reach the cortex through VPL. These are fed into the primary motor area via the primary sensory area, especially its anterior portion, corresponding to Brodmann areas 3 and 1 (possibly also area 2), without involving other cortical regions. The spinothalamic tract and direct thalamic inputs into the motor cortex do not contribute much to this effect. Some patients could generate voluntary movements despite the absence of the facilitatory effect. The present method will enable us to investigate in humans the function of one of the somatotopically organized sensory feedback input pathways into the motor cortex, and will be useful in monitoring ongoing finger movements during object manipulation.

The persistent vegetative state after closed head injury: clinical and magnetic resonance imaging findings in 42 patients.

OBJECT: In this retrospective study, the authors analyzed the frequency, anatomical distribution, and appearance of traumatic brain lesions in 42 patients in a posttraumatic persistent vegetative state. METHODS: Cerebral magnetic resonance (MR) imaging was used to detect the number of lesions, which ranged from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases there was evidence on MR imaging of diffuse axonal injury, and injury to the corpus callosum was detected in all patients. The second most common area of diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem (74% of patients). In addition, 65% of these patients exhibited white matter injury in the corona radiata and the frontal and temporal lobes. Lesions to the basal ganglia or thalamus were seen in 52% and 40% of patients, respectively. Magnetic resonance imaging showed some evidence of cortical contusion in 48% of patients in this study; the frontal and temporal lobes were most frequently involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in this subgroup there was an 80% incidence of contralateral peduncular lesions in the midbrain. The most common pattern of injury (74% in this series) was the combination of focal lesions of the corpus callosum and the dorsolateral brainstem. In patients with no evidence of diffuse axonal injury in the upper brainstem (26% in this series), callosal lesions were most often associated with basal ganglia lesions. Lesions of the corona radiata and lobar white matter were equally distributed in patients with or without dorsolateral brainstem injury. Moreover, cortical contusions and thalamic, parahippocampal, and cerebral peduncular lesions were also similarly distributed in both groups. CONCLUSIONS: The data indicate that diffuse axonal injury may be the major form of primary brain damage in the posttraumatic persistent vegetative state. In addition, the authors demonstrated in this study that MR imaging, in conjunction with a precise clinical correlation, may provide useful supportive information for the accurate diagnosis of a persistent vegetative state after traumatic brain injury.

Neglected spinal cord, brain stem and musculoskeletal injuries stemming from birth trauma.

OBJECTIVE: A review of the medical literature was undertaken to determine cause, diagnosis, prognosis, treatment and prevention of injuries resulting from birth trauma. The primary focus was the neonate, though infant, child and adult were also considered because the effects of birth trauma can be life-long. DATA SOURCE: A compilation of case studies and review articles were extracted from numerous "MEDLINE" literature searches. Key Terms included: Birth Trauma, Central Nervous System Injuries, Musculoskeletal Injuries, Stillbirth, Sudden Infant Death Syndrome (SIDS), Cerebral Palsy, Brachial Plexus Palsies (Erb's and Klumpke's), Neonatal-Infantile Respiratory Distress, Obstetric Accidents (Forceps, Vacuum Cup and Cesarean Deliveries), Subluxation, Chiropractic Treatment. American, British, Danish and German studies were included to show the universality of the problem. STUDY SELECTION: Findings were selected on the basis of a clear connection between birth trauma and the resulting symptoms, syndromes and/or death. DATA EXTRACTION: Findings were compiled by studying articles from the literature search. The quality and validity were assessed by corresponding references, method of documentation, number of case studies, length of time over which studies took place and presence of follow-up documentation. DATA SYNTHESIS: Inadequacies and source discrepancies were also included with regard to cause and types of obstetric accidents. CONCLUSION: Birth trauma remains an underpublicized and, therefore, an undertreated problem. There is a need for further documentation and especially more studies directed toward prevention. In the meantime, manual treatment of birth trauma injuries to the neuromusculoskeletal system could be beneficial to many patients not now receiving such treatment, and it is well within the means of current practice in chiropractic and manual medicine.

Defective thermoregulation after traumatic brain injury. A single subject evaluation.

Central fever is a known complication of traumatic brain injury (TBI), particularly in association with brain stem involvement. Chronic deficits in thermoregulation after TBI have not been reported. We describe a patient who had central fevers acutely after injury, but developed intermittent temperature elevations during thermal stress in the post-acute phase. A prospective evaluation of the patient's temperature control was conducted. The patient stayed in the laboratory for two half-day evaluation sessions. On the first day, the room temperature was raised by 10 degrees F each hour and rectal temperature was recorded hourly. On the second day, the room temperature was lowered by 10 degrees each hour in a similar fashion. The patient's core temperature rose above normal in the warm environment but did not drop in the cold environment. This suggests that the patient had a chronic deficit in either sensing temperature elevations or activating heat dissipation mechanisms under thermal stress.

Production of generalized learning deficit and permanent growth stunting by bilateral brain stem lesions.

Bilateral lesions of the globus pallidus, ventrolateral thalamus, substantia nigra, or the median raphe produce a generalized learning deficit in rats. Bilateral lesions of the dorsomedial hypothalamic nuclei stunt growth in rats without significantly disturbing endocrine functions and without producing a generalized learning deficit. Globus pallidus, ventrolateral thalamus, substantia nigra, median raphe, and dorsomedial hypothalamic nuclei lesions were produced in weanling Sprague-Dawley rats to compare their effect on physical growth. At approximately 72 d of age, all lesions had resulted in reduced body wt, tail length, and tibial length. The differences lacked significance only in body wt after median raphe lesions and tail length after ventrolateral thalamus lesions. In rats with the generalized learning deficit, body size was most stunted after substantia nigra lesions. Tibial epiphyseal width was modestly increased in rats with the generalized learning deficit. Food intake/average body wt ratio in substantia nigra and dorsomedial hypothalamic nuclei rats did not differ significantly from control values. Decreases in brain, heart, liver, kidney, and testes tended to occur after all the lesions, but brain and testis organ wt/body wt ratios were either increased or unchanged. We conclude that brain lesions producing a generalized learning deficit in rats result in impaired physical growth. The results indicated that the stunted animals maintain adequate food intake and have normal growth hormone function. The anatomical substrate for generalized learning impairment may overlap with that of a set point for body size.

Electrophrenic respiration in patients with craniocervical trauma.

We implanted electrophrenic respiration (EPR) units in 15 apneic quadriplegic patients with brain stem or high cervical cord injury. 11 of the patients achieved full-time respiration with EPR and another 2 achieved half-time respiration. Despite the loss of patients due to unrelated problems, 7 now use EPR continuously, 1 for 18 years. The factors involved in the significant success rate with EPR are discussed from the point of view of a neurosurgeon.