Near-total absence of REM sleep co-occurring with normal cognition: an update of the 1984 paper.

BACKGROUND: REM sleep (REMS) is considered vital for supporting well-being and normal cognition. However, it remains unclear if and how decreases in REMS impair cognitive abilities. Rare case studies of patients with REMS abolishment due to pontine lesions remain sporadic, and formal evaluation of cognitive status is lacking. In 1984, Lavie and colleagues described the case of Y.C. - a man with a pontine lesion and near-total absence of REMS who led a normal life. Here, we set out to re-evaluate this individual's REMS status 30 years after the original report, and formally assess his cognitive abilities. METHODS: Four whole-night polysomnographic sleep recordings were conducted to evaluate sleep architecture. Sleep scoring was performed according to the American Academy of Sleep Medicine (AASM) guidelines. Cranial Computed Tomography (CT) imaging was performed, as well as formal neuropsychological testing to evaluate cognitive functions. RESULTS: Y.C. averaged 4.5% of sleep time in REMS, corresponding to the 0.055 percentile of normal values for his age. Furthermore, residual REMS episodes were short and only occurred towards the end of the night. CT imaging revealed damage and metallic fragments in pons, cerebellum, and thalamus. Neuropsychological evaluation demonstrated average to high-average cognitive skills, normal memory, and motor difficulties including speech and left hand dyspraxia. CONCLUSIONS: To our knowledge, this is the only case where REMS loss resulting from pontine lesion was re-evaluated after many years. We find a near-total absence of REMS with no signs of significant compensation throughout adult life, along with normal cognitive status. The results provide a unique perspective on the ongoing debate regarding the functional role of REMS in supporting cognition.

Injury of the cortico-ponto-cerebellar tract in a patient with mild traumatic brain injury: A case report.

RATIONALE: We report on a patient with injury of the cortico-ponto-cerebellar tract (CPCT) following mild traumatic brain injury (TBI), diagnosed by diffusion tensor tractography (DTT). PATIENT CONCERNS: A 53-year-old female patient was injured in a car crash. While under treatment at a local medical center for headache, mild motor weakness, and cognitive impairment that developed following the car crash, she fell, hitting her head on the ground, about six weeks after the car crash. DIAGNOSES: Approximately three months after the car crash, she began to show tremor on both hands and mild truncal ataxia. Twenty months after the car crash, when she underwent neurological evaluation at the rehabilitation department of a university hospital, she presented with mild resting and intentional tremor on both hands, and mild truncal ataxia. INTERVENTIONS: N/A. OUTCOMES: On 20-month DTT, the left CPCT showed tearing at the level of the subcortical white matter and pons, and discontinuation at the cerebellar portion. However, the integrity of the DRTT was well-preserved in both hemispheres. LESSONS: Using DTT, injury of the CPCT was demonstrated in a patient with ataxia and tremor following mild TBI.

Role of A5 noradrenergic neurons in the chemoreflex control of respiratory and sympathetic activities in unanesthetized conditions.

The A5 area at the ventrolateral pons contains noradrenergic neurons connected with other medullary areas involved in the cardiorespiratory control. Its contribution to the cardiorespiratory regulation was previously evidenced in anesthetized conditions. In the present study, we investigated the involvement of the A5 noradrenergic neurons to the basal and chemoreflex control of the sympathetic and respiratory activities in unanesthetized conditions. A5 noradrenergic neurons were lesioned using microinjections of anti-dopamine ß-hydroxylase saporin (anti-DßH-SAP). After 7-8days, we evaluated the arterial pressure levels, heart rate and minute ventilation in freely moving adult rats (280-350g) as well as recorded from thoracic sympathetic (tSN) and phrenic nerves (PN) using the arterially perfused in situ preparation of juvenile rats (80-90g). Baseline cardiovascular, sympathetic and respiratory parameters were similar between control (n=7-8) and A5-lesioned rats (n=5-6) in both experimental preparations. In adult rats, lesions of A5 noradrenergic neurons did not modify the reflex cardiorespiratory adjustments to hypoxia (7% O2) and hypercapnia (7% CO2). In the in situ preparations, the sympatho-excitation, but not the PN reflex response, elicited by either the stimulation of peripheral chemoreceptors (ΔtSN: 110±12% vs 58±8%, P<0.01) or hypercapnia (ΔtSN: 9.5±1.4% vs 3.9±1.7%, P<0.05) was attenuated in A5-lesioned rats compared to controls. Our data demonstrated that A5 noradrenergic neurons are part of the circuitry recruited for the processing of sympathetic response to hypoxia and hypercapnia in unanesthetized conditions.

Management Strategy of a Transorbital Penetrating Pontine Injury by a Wooden Chopstick.

BACKGROUND: Transorbital penetrating pontine injuries from small spear-like objects, which are extremely rare, provide neurosurgeons with life-threatening and challenging conditions to manage. CASE DESCRIPTION: We present an unusual case of transorbital penetrating pontine injury and discuss imaging, diagnosis, management strategy, and anatomy-injury correlation. A 23-year-old man sustained a penetrating cranial injury from a bamboo chopstick that extended from the right orbit to the pons and cerebellum. Using a frontotemporal approach, we successfully removed the chopstick. Follow-up studies confirmed a good outcome. CONCLUSIONS: Preoperative imaging, correct diagnosis, and surgical treatment are necessary to manage transorbital penetrating pontine injuries caused by spear-like objects, with specific attention paid to effective exposure and inventive means with total removal of the foreign object without causing further injury. A trajectory through the superior orbital fissure and paralateral to the cavernous sinus and into the pons seems to be the most prevalent and influences management of removal and injuries.

Predictors of Surgical Results in Patients with Primary Pontine Hemorrhage.

AIM: Prediction of outcome for surgical patients with primary pontine hemorrhage (PPH) is seldom reported although many predictors from clinical and radiological features have been identified in conservative patients. The purpose of this study was to assess the prognostic factors affecting the 30-day mortality and 3-month functional outcome in surgical patients after PPH. MATERIAL AND METHODS: Forty-five patients with large PPH ( > 5 ml) and Glasgow Coma Scale (GCS) score < 8 were treated surgically at West China Hospital. The demographic, clinical, imaging and follow-up data were collected retrospectively. Factors affecting the mortality and functional outcome were statistically analyzed. RESULTS: Fourteen patients (31.1%) died within 30 days and 7 patients (15.6%) gained a favorable functional recovery within 3 months. A multivariate analysis showed that the hematoma volume, GCS score on admission, age, and type of hemorrhage were all significantly related to the 30-day mortality, while the hematoma volume, GCS score on admission, rostrocaudal extension were associated with the 3-month functional outcome. The presence of hydrocephalus was not found responsible for the surgical outcomes. CONCLUSION: The identification of these prognostic factors is helpful for selecting the candidates for surgical treatment. Those with younger age, smaller hematoma without rostrocaudal extension, unilateral hemorrhage, and higher GCS score may benefit from surgery.

A posttraumatic pontomedullary rent with good outcome.

Posttraumatic pontomedullary rents have been described mainly as postmortem histopathological findings in patients who died immediately or within the first hours after trauma. To the best of our knowledge, no long-term survivors of this condition have been described, and those surviving initially were always severely impaired. We present the first patient with this condition and with corresponding lesions on imaging who survived longer than 3 months. Moreover, the patient regained almost complete independence 1 year after the trauma. We briefly discuss the proposed mechanisms of this injury. We conclude that this lesion, when incomplete, is not always lethal and can exceptionally have a good clinical outcome. Prevention of respiratory failure is of utmost importance in these patients.

Síndrome de enclaustramiento: presentación de un caso / Locked-in syndrome: case report

El síndrome de enclaustramiento (Locked-in syndrome) es una entidad neurológica altamente discapacitante, producida por lesiones en la porción ventral de la protuberancia; de etiología principalmente vascular. Clínicamente se manifiesta por tetraplejía, anartria, preservación de la conciencia y capacidad de expresarse mediante movimientos oculares. Presentamos el caso de un paciente masculino de 33 años, transferido de otra institución de salud con un cuadro clínico progresivo y poco específico, caracterizado principalmente por deterioro del estado de conciencia, dificultad respiratoria, cefalea de intensidad moderada y vómitos. Mediante pruebas de imágenes se comprobó la presencia de un área de isquemia en la región irrigada por el sistema vertebrobasilar. Se realizó un enfoque diagnóstico y terapéutico invasivo de orden endovascular.

Locked-in syndrome is a highly disabling neurological entity, due to lesions in the ventral portion of the pons, mainly vascular etiology. Clinical features are quiadriplegia, anarthria, preservation of consciousness and the ability to express by ocular movements. We shown a case of a 33 years-old man, who was transfer from another institution with a progressive and poorly specific clinical manifestations, mainly characterized by diminishing of consciousness, breathing difficulty, headache and vomiting, with the presumptive diagnosis of central nervous system infection. We performed image diagnostic tests and they shown and ischemic feature in the region of the vertebrobasilar irrigation. It was perform an endovascular diagnostic therapeutic approach.

Deafferentation in thalamic and pontine areas in severe traumatic brain injury.

PURPOSE: Severe traumatic brain injury (TBI) is characterized mainly by diffuse axonal injuries (DAI). The cortico-subcortical disconnections induced by such fiber disruption play a central role in consciousness recovery. We hypothesized that these cortico-subcortical deafferentations inferred from diffusion MRI data could differentiate between TBI patients with favorable or unfavorable (death, vegetative state, or minimally conscious state) outcome one year after injury. METHODS: Cortico-subcortical fiber density maps were derived by using probabilistic tractography from diffusion tensor imaging data acquired in 24 severe TBI patients and 9 healthy controls. These maps were compared between patients and controls as well as between patients with favorable (FO) and unfavorable (UFO) 1-year outcome to identify the thalamo-cortical and ponto-thalamo-cortical pathways involved in the maintenance of consciousness. RESULTS: Thalamo-cortical and ponto-thalamo-cortical fiber density was significantly lower in TBI patients than in healthy controls. Comparing FO and UFO TBI patients showed thalamo-cortical deafferentation associated with unfavorable outcome for projections from ventral posterior and intermediate thalamic nuclei to the associative frontal, sensorimotor and associative temporal cortices. Specific ponto-thalamic deafferentation in projections from the upper dorsal pons (including the reticular formation) was also associated with unfavorable outcome. CONCLUSION: Fiber density of cortico-subcortical pathways as measured from diffusion MRI tractography is a relevant candidate biomarker for early prediction of one-year favorable outcome in severe TBI.

Selective lesioning of nucleus incertus with corticotropin releasing factor-saporin conjugate.

The nucleus incertus (NI), a brainstem nucleus found in the pontine periventricular grey, is the primary source of the neuropeptide relaxin-3 in the mammalian brain. The NI neurons have also been previously reported to express several receptors and neurotransmitters, including corticotropin releasing hormone receptor 1 (CRF1) and gamma-aminobutyric acid (GABA). The NI projects widely to putative neural correlates of stress, anxiety, depression, feeding behaviour, arousal and cognition leading to speculation that it might be involved in several neuropsychiatric conditions. On the premise that relaxin-3 expressing neurons in the NI predominantly co-express CRF1 receptors, a novel method for selective ablation of the rat brain NI neurons using corticotropin releasing factor (CRF)-saporin conjugate is described. In addition to a behavioural deficit in the fear conditioning paradigm, reverse transcriptase polymerase chain reaction (RT-PCR), western blotting (WB) and immunofluorescence labelling (IF) techniques were used to confirm the NI lesion. We observed a selective and significant loss of CRF1 expressing cells, together with a consistent decrease in relaxin-3 and GAD65 expression. The significant ablation of relaxin-3 positive neurons of the NI achieved by this lesioning approach is a promising model to explore the neuropsychopharmacological implications of NI/relaxin-3 in behavioural neuroscience.

Downbeat nystagmus associated with damage to the medial longitudinal fasciculus of the pons: a vestibular balance control mechanism via the lower brainstem paramedian tract neurons.

The paramedian tract (PMT) neurons, a group of neurons associated with eye movement that project into the cerebellar flocculus, are present in or near the medial longitudinal fasciculus (MLF) in the paramedian region of the lower brainstem. A 66-year-old man with multiple sclerosis in whom downbeat nystagmus appeared along with right MLF syndrome due to a unilateral pontomedullary lesion is described. In light of these findings, a possible schema for the vestibular balance control mechanism circuit of the PMT neurons via the flocculus is presented. Damage to the PMT neurons impaired the elective inhibitory control mechanism of the anterior semicircular canal neural pathway by the flocculus. This resulted in the appearance of anterior semicircular canal-dominant vestibular imbalance and the formation of downbeat nystagmus. From the pathogenesis of this vertical vestibular nystagmus, the action of the PMT neurons in the vestibular eye movement neuronal pathway to maintain vestibular balance was conjectured to be as follows. PMT neurons transmit vestibular information from the anterior semicircular canals to the cerebellum, forming a cerebellum/brainstem feedback loop. Vestibular information from that loop is integrated in the cerebellum, inhibiting only the anterior semicircular canal neuronal pathway via the flocculus and controlling vestibular balance.

The prognostic significance of traumatic brainstem injury detected on T2-weighted MRI.

OBJECT: Magnetic resonance imaging is frequently used to evaluate patients with traumatic brain injury in the acute and subacute setting, and it can detect injuries to the brainstem, which are often associated with poor outcomes. This study was undertaken to determine which MRI and clinical factors provide prognostic information in patients with traumatic brainstem injuries. METHODS: The authors performed a retrospective analysis of cases involving patients admitted to a Level I trauma center who were identified in a prospective database as having suffered traumatic brainstem injury identified on MRI. Patient outcomes were dichotomized to dead/vegetative versus functional groups. Standard demographic data, admission Glasgow Coma Scale (GCS) scores, results of the motor component of the GCS examination at admission and 24 hours later, CT scan findings, and peak intracranial pressure were collected from medical records. Volumetric analysis of each patient's injuries was performed with T2-weighted and gradient echo sequences. The T2-weighted MRI sequence for each patient was reviewed to determine the anatomical location of injury within the brainstem and whether the injury crossed the midline. RESULTS: Thirty-six patients who met the study inclusion criteria were identified. At 6-month follow-up, 53% of these patients had poor outcomes and 47% had recovered. Patients with injuries to the medulla or deep bilateral injuries to the pons did not recover. The T2 volumes were found superior to gradient echo sequences in regard to predicting survival (ROC/AUC 0.67, p = 0.07 vs 0.60, p = 0.29, respectively), but neither reached statistical significance. The timing of MR image acquisition did not influence the findings. The time from admission to MRI did not differ significantly between the recovered group and the poor-outcome group (p = 0.52, Mann-Whitney test), and lesion size as measured by T2 volume did not vary with time to scan (R(2) = 0.03, p = 0.3, linear regression). Performing a stepwise logistic regression with all the variables yielded the following factors related to recovery: crossing midline, p = 0.0156, OR 0.075; and 24-hour GCS motor score, p = 0.0045, OR = 2.25, c-statistic 0.913. Further examination of these 2 factors disclosed the following: none of 15 patients with midline-crossing lesions and a 24-hour GCS motor score of 4 or less recovered; conversely, 12 of 13 patients with lesions that did not cross midline recovered, regardless of GCS motor score. CONCLUSIONS: Bilateral injury to the pons and medulla as detected on T2-weighted MRI sequences was associated with poor outcome in patients with brainstem injuries; T2 volumes were found superior to gradient echo sequences in regard to predicting survival, but neither reached statistical significance. When MRI findings were coupled with clinical examination findings, a strong correlation existed between poor outcome and the combination of bilateral brainstem injury and a motor GCS score of 4 or less 24 hours after admission.

Spinal and pontine relay pathways mediating respiratory rhythm entrainment by limb proprioceptive inputs in the neonatal rat.

The coordination of locomotion and respiration is widespread among mammals, although the underlying neural mechanisms are still only partially understood. It was previously found in neonatal rat that cyclic electrical stimulation of spinal cervical and lumbar dorsal roots (DRs) can fully entrain (1:1 coupling) spontaneous respiratory activity expressed by the isolated brainstem/spinal cord. Here, we used a variety of preparations to determine the type of spinal sensory inputs responsible for this respiratory rhythm entrainment, and to establish the extent to which limb movement-activated feedback influences the medullary respiratory networks via direct or relayed ascending pathways. During in vivo overground locomotion, respiratory rhythm slowed and became coupled 1:1 with locomotion. In hindlimb-attached semi-isolated preparations, passive flexion-extension movements applied to a single hindlimb led to entrainment of fictive respiratory rhythmicity recorded in phrenic motoneurons, indicating that the recruitment of limb proprioceptive afferents could participate in the locomotor-respiratory coupling. Furthermore, in correspondence with the regionalization of spinal locomotor rhythm-generating circuitry, the stimulation of DRs at different segmental levels in isolated preparations revealed that cervical and lumbosacral proprioceptive inputs are more effective in this entraining influence than thoracic afferent pathways. Finally, blocking spinal synaptic transmission and using a combination of electrophysiology, calcium imaging and specific brainstem lesioning indicated that the ascending entraining signals from the cervical or lumbar limb afferents are transmitted across first-order synapses, probably monosynaptic, in the spinal cord. They are then conveyed to the brainstem respiratory centers via a brainstem pontine relay located in the parabrachial/Kölliker-Fuse nuclear complex.

Juxtapontine abscess around a retained wooden fragment following a penetrating eye injury: surgical management via a transtentorial approach.

Penetrating injury through the orbit with a retained intracranial wooden foreign body is rare. The authors report the case of a child with a juxtapontine brain abscess secondary to a retained foreign body. The pitfalls in diagnosis and the surgical management for removal of the wooden fragment and drainage of the abscess are discussed.

Pontomedullary lacerations in unhelmeted motorcyclists and bicyclists: a retrospective autopsy study.

Pontomedullary lacerations (PMLs) have often been reported in car occupants and pedestrians, are less frequently described in motorcyclists, and are very rarely described in bicyclists. The aim of this study was to determine the frequency of brainstem PMLs among fatally injured motorcyclists and bicyclists as well as the frequency of concomitant cranial, facial, and cervical spine injuries in such cases. A possible underlying mechanism of PML in fatally injured motorcyclists and bicyclists might thus be established. Of 443 cases of fatally injured motorcyclists and bicyclists, a sample of 381 cases of fatally injured motorcyclists and bicyclists with head injury of Abbreviated Injury Scale score of 3 or greater was formed and further analyzed. This group was composed of 345 men and 36 women. The average age was 48.8 ± 20.8 years (range, 15-99 years). In the analyzed sample group, there were 158 motorcyclists and 223 bicyclists. Partial PMLs were present in 44 cases (12%) within the sample of 381 head injuries, which breaks down to 40 men and 4 women. In our study, the impact area on the head and the specific skull base fracture type were good predictors of either PML occurrence or absence (B = -2.036, Wald = 161.312, P < 0.01, for the whole model). Impact to the chin, with or without a skull base fracture, most often led to this fatal injury due to impact force transmission, either through jawbone or vertebral column. Also, lateral head impact, the most frequent in bicyclists, with subsequent hinge fracture, PML, and frontoposterior hyperextension of the head that is associated with upper spine fracture, could be possible mechanisms of brainstem injury in fatally injured motorcyclists or bicyclists. Our study showed that the jawbone, as well as other facial bones, could act as shock absorbers, and their fracture could diminish energy transfer toward the skull and protect the brain and brainstem from injury.

Pontine and thalamic influences on fluid rewards: II. Sucrose and corn oil conditioned aversions.

In this study conditioned aversions were produced in sham feeding rats to limit postingestive feedback from the oral stimulus. All control rats learned an aversion to either 100% corn oil or 0.3 M sucrose when ingestion of these stimuli was followed by an injection of lithium chloride (LiCl). Rats with lesions of the ventroposteromedial thalamus also learned to avoid either corn oil or sucrose. After 3 trials, rats with damage to the parabrachial nuclei (PBN) learned to avoid 100% corn oil, but failed to do so when the stimulus was 0.3 M sucrose. These results support our hypothesis that the PBN is necessary to appropriately respond to a taste, but not an oil cue as a function of experience (i.e., pairings with LiCl). The results also are consistent with our results from operant tasks demonstrating that the trigeminal thalamus, the ventroposteromedial nucleus, is not required for responding to the rewarding properties of sucrose, oil, or for modifying the response to these stimuli as a function of experience.

Pontine and thalamic influences on fluid rewards: III. Anticipatory contrast for sucrose and corn oil.

An anticipatory contrast effect (ACE) occurs when, across daily trials, an animal comes to respond less than normally to a first stimulus when it is followed shortly by a second, more preferred solution. Classically, ACE is studied using a low (L) concentration of saccharin or sucrose, followed by access to a higher (H) concentration of sucrose. Subjects in the control condition have two bouts of access to the weaker solution presented on the same schedule. The ACE is measured by the difference in intake of the first bout low solution between subjects in the low-low (L-L) vs. the low-high (L-H) conditions. Here we used this paradigm with sham feeding rats and determined that nutritional feedback was unnecessary for the development of ACE with two concentrations of sucrose or with two concentrations of corn oil. Next we showed that ibotenic acid lesions centered in the orosensory thalamus spared ACEs for both sucrose and corn oil. In contrast, lesions of the pontine parabrachial nuclei (PBN), the second central relay for taste in the rat, disrupted ACEs for both sucrose and corn oil. Although the sensory modalities needed for the oral detection of fats remain controversial, it appears that the PBN is involved in processing the comparison of disparate concentrations of sucrose and oil reward.