Emergency Neurological Life Support: Spinal Cord Compression (SCC)

Acute spinal cord compression (SCC) is the most serious of the diseases of the cord and should be accorded special attention in neurocritical care. Patients with SCC have a combination of motor and sensory dysfunction that has a distribution referable to one, or a few contiguous, spinal levels. Bowel and bladder dysfunction and neck or back pain are usually part of the clinical presentation but are not uniformly present. Because interventions are time-sensitive, the recognition and treatment of SCC was chosen as an ENLS protocol.     

Emergency Neurologic Life Support: Spinal Cord Compression

There are many causes of acute myelopathy including multiple sclerosis, systemic disease (SD), and acute spinal cord compression (SCC). SCC should be among the first potential causes considered given the significant permanent loss of neurologic function commonly associated with SCC. This impairment can occur over a short period of time, and may be avoided through rapid and acute surgical intervention. Patients with SCC typically present with a combination of motor and sensory dysfunction that has a distribution referable to a spinal level. Bowel and bladder dysfunction and neck or back pain may also be part of the clinical presentation, but are not uniformly present. Because interventions are critically time-sensitive, the recognition and treatment of SCC was chosen as an ENLS protocol.     

Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex.

OBJECTIVE: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. METHOD: Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. RESULTS: One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. CONCLUSIONS: High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.     

Compartment Syndrome of the Foot After Calcaneal Fracture

Background: Compartment syndrome of the foot as a result of a calcaneal fracture has received only occasional consideration in the recent Emergency Medicine literature, yet it remains a challenging diagnosis to make. The devastating consequences of untreated compartment syndrome of the foot include clawing of the lesser toes, stiffness, chronic pain, motor weakness, neurovascular dysfunction, and fixed deformities of the foot. In addition to decreased quality of life, this also leads to lost time at work and lost wages. Calcaneal fractures can lead to devastating long-term disability that is often permanent and life-altering for patients suffering from this injury. Approximately 10% of patients with these fractures develop compartment syndrome of the foot. The pathogenesis of calcaneal fractures is well recognized, and the surgical treatment techniques continue to evolve. Objectives: The objectives of this case report are to increase understanding of the pathophysiology of compartment syndrome and its short- and long-term consequences, to improve the ability to diagnose compartment syndrome, and to emphasize the need for emergent surgical treatment. Case Report: A 37-year-old man sustained an isolated comminuted, extra-articular calcaneus fracture that resulted in compartment syndrome of the foot. The diagnosis required measurement of several compartments in the foot. He subsequently received emergent operative decompression and experienced a positive outcome. Conclusion: Diagnosis of compartment syndrome of the foot is a clinical one, and diagnostic tools such as radiographic imaging and compartment pressure monitoring can help confirm the diagnosis. It is also important to understand the long-term sequelae of this injury and to involve a specialist early in the decision-making and treatment process.     

Opposing effects of striatonigral feedback pathways on midbrain dopamine cell activity

The existence of a striatonigral GABAergic pathway has been well established both anatomically and biochemically. During intracellular recording from identified DA neurons in vivo, stimulation of the striatum (100 microA, 50 microseconds pulses) elicits an inhibitory postsynaptic potential (IPSP) and a rebound depolarization. The IPSP is a short latency (1.8-2.2 ms) conductance increase to chloride, since: the reversal potential is near the chloride reversal potential reported for other cells (-68 mV); intracellular chloride injection progressively reverses the IPSP into a depolarization with a similar time course; and the response of DA cells to systemic injection of the chloride channel blocker, picrotoxin, also exhibits a similar reversal potential. In contrast, during extracellular recording, stimulation of the striatum at low levels of intensity (e.g. 20 microA at 10 Hz) increases the firing rate of DA cells. Stimulation of the striatum will, in addition, elicit IPSPs in a subclass of substantia nigra zona reticulata neurons at the same latency as the IPSPs triggered in DA cells. These IPSPs also reverse with intracellular chloride injection. However, their amplitude is larger and their duration longer than observed in DA cells, and there is no depolarizing rebound. The late component of the IPSP in the zona reticulata neurons corresponds temporally to the rebound depolarization seen in DA cells in response to striatal stimulation. In addition, when recorded extracellularly, striatal stimulation will inhibit the firing of this class of zona reticulata interneurons at the same stimulation parameters that will excite DA cells. These data suggest that striatal cells may send branched fast-conducting GABAergic projections to zona reticulata cells and DA cells. Furthermore, low levels of striatal stimulation can excite DA cells by preferentially inhibiting interneurons in the zona reticulata which are more sensitive to the inhibitory effects of GABA than are DA neurons.     

The control of firing pattern in nigral dopamine neurons: single spike firing

Dopamine (DA) neurons have been recorded in vivo in four states of activity: hyperpolarized, nonfiring; single spike firing; burst firing; and depolarization inactivation. Nonfiring DA neurons can be made to fire by iontophoretic application of the excitatory substances glutamate and cholecystokinin, or by depolarizing current injection. Spontaneously active DA cells typically fire in a slow (3 to 8 Hz) irregular pattern. In vivo intracellular recordings revealed that this pattern is sustained by the alternation of two currents: a spontaneously occurring slow depolarization (13 +/- 3 mV amplitude, 78 +/- 40 msec duration) which brings the membrane potential of the DA cell to spike threshold (-42 mV), and an afterhyperpolarization mediated by a calcium-activated potassium conductance (IK(Ca)). The slow depolarization is a pacemaker-like conductance, with a rate of rise proportional to the membrane potential. The regular pacemaker pattern of the spontaneously occurring slow depolarization is interrupted by the IK(Ca) which appears to be triggered by calcium entry during the action potential. Thus, intracellular injection of the calcium chelator EGTA will cause DA cells to fire in a regular, pacemaker pattern. The IK(Ca) is observed after single spikes and trains of spikes with the amplitude of the afterhyperpolarization being proportional to the number of spikes in a train. Both the afterhyperpolarization and the firing accommodation observed during depolarizing current injection can be blocked by intracellular injection of the calcium chelator EGTA.     

Paradoxical GABA excitation of nigral dopaminergic cells: indirect mediation through reticulata inhibitory neurons

Biochemical and electrophysiological and electrophysiological studies suggest that GABA agonists increase the activity of dopaminergic neurons in the zona compacta (ZC) of the substantia nigra despite a known GABAergic input to ZC cells. Using single-unit recording techniques we have investigated this "paradoxical" effect. One population of neurons located in the zona reticulata (ZR) of the substantia nigra was found to be 20 times more sensitive to iontophoretically applied GABA than ZC neurons. GABA introduced by means of microiontophoresis into the ZR caused an increase in ZC cell activity while glutamic acid introduced in the same manner produced an inhibition of ZC cells. The latter effect was blocked by low doses of picrotoxin. Muscimol (i.v.) caused a decrease in ZR cell activity at the same dose that caused a parallel increase in ZC cell firing rate. These data suggest that ZC cells receive an inhibitory GABAergic input from ZR cells that are in turn inhibited by low doses of GABA agonists. Such an anatomical arrangement would account for the "paradoxical" excitatory effect of GABA agonists on ZC neuron activity.     

Evidence for the absence of impulse-regulating somatodendritic and synthesis-modulating nerve terminal autoreceptors on subpopulations of mesocortical dopamine neurons

Electrophysiological and biochemical techniques were used to study midbrain dopamine systems. In the electrophysiological studies, projection areas of individual dopaminergic cells were identified by antidromic activation. Dopamine cells which innervate the piriform cortex and those that innervate the caudate nucleus demonstrated their usual dose-dependent inhibitory response to both the intravenous administration of the direct-acting dopamine agonist apomorphine and the microiontophoretic application of dopamine. In contrast, the firing rate of dopamine neurons which project to the prefrontal cortex and of those terminating in the cingulate cortex was not altered by either the intravenous administration of low to moderate doses of apomorphine or microiontophoretically applied dopamine. The mean basal discharge rate and degree of burst firing was also different between these subgroups of midbrain dopaminergic neurons. Mesoprefrontal and mesocingulate dopamine neurons had mean firing rates of 9.3 and 5.9 spikes/s respectively, and showed intense burst activity. Mesopiriform and nigrostriatal dopamine cells had discharge rates of 4.3 and 3.1 spikes/s and displayed only moderate bursting. The dopaminergic nature of those mesocortical neurons insensitive to apomorphine and dopamine was confirmed using combined intracellular recording and catecholamine histofluorescence techniques. Thus, after the intracellular injection of colchicine and subsequent processing for glyoxylic acid-induced histofluorescence, the injected cells could be identified by their brighter fluorescences compared to the surrounding, normally fluorescing, non-injected dopamine neurons. Using biochemical techniques, subgroups of midbrain dopaminergic systems were again found to differ. The administration of gamma-butyrolactone increased dopamine levels in all areas sampled (prefrontal, cingulate and piriform cortices as well as the caudate nucleus). However, although this effect was readily reversed in both the piriform cortex and caudate nucleus by pretreatment with apomorphine, this treatment had no effect on the increased dopamine levels observed in the prefrontal and cingulate cortices. In addition, the decline in dopamine levels after synthesis inhibition with alpha-methyltyrosine was significantly faster in the prefrontal and cingulate cortices relative to the caudate nucleus. The piriform cortex showed an intermediate decline which was not significantly different from that observed in any of the other regions.(ABSTRACT TRUNCATED AT 400 WORDS)