Tatsuro Kawamata, Tatsuro Mori, Shoshi Sato and Yoichi Katayama
Severe cerebral contusion is often associated with nonhemorrhagic mass effect that progresses rapidly within 12 to 48 hours posttrauma. The mechanisms underlying such a rapid progression of mass effect cannot be fully explained by classic concepts of vasogenic and cytotoxic brain edema. Data from previous clinical trials, including diffusion-weighted magnetic resonance imaging studies, have indicated that cells in the central (core) area of the contusion undergo shrinkage, disintegration, and homogenization, whereas cellular swelling is located predominately in the peripheral (rim) area during this period. The authors hypothesized that high osmolality within the contused brain tissue generates an osmotic potential across the central and peripheral areas or causes blood to accumulate a large amount of water. To elucidate the role of tissue osmolality in contusion edema, they investigated changes in tissue osmolality, specific gravity, and ion concentration in contused brain in both experimental and clinical settings. Their results demonstrated that cerebral contusion induced a rapid increase in tissue osmolality from a baseline level of 311.4 ± 11.3 to 402.8 ± 15.1 mOsm at 12 hours posttrauma (p < 0.0001). Specific gravity in tissue significantly decreased from 1.0425 ± 0.0026 to 1.0308 ± 0.0028 (p < 0.01), reflecting water accumulation in contused tissue. The total ionic concentration [Na+] + [K+] + [Cl−] did not change significantly at any time point. Inorganic ions do not primarily contribute to this elevation in osmolality, suggesting that the increase in colloid osmotic pressure through the metabolic production of osmoles or the release of idiogenic osmoles can be a main cause of contusion edema.
Yoichi Katayama, Chikashi Fukaya and Takamitsu Yamamoto
Object. The goal of this study was to identify the neurological characteristics of patients with poststroke pain who show a favorable response to motor cortex (MC) stimulation used to control their pain.
Methods. The neurological characteristics of 31 patients treated by MC stimulation were analyzed. In 15 patients (48%), excellent or good pain control (pain reduction > 60%) was achieved for follow-up periods of more than 2 years by using MC stimulation at intensities below the threshold for muscle contraction. Satisfactory pain control was achieved in 13 (73%) of 18 patients in whom motor weakness in the painful area was virtually absent or mild, but in only two (15%) of the 13 patients who demonstrated moderate or severe weakness in the painful area (p < 0.01). Muscle contraction was inducible in the painful area in 20 patients when stimulated at a higher intensity. No such muscle response was inducible in the remaining 11 patients, no matter how extensively the authors attempted to determine appropriate stimulation sites. Satisfactory pain control was achieved in 14 (70%) of the 20 patients in whom muscle contraction was inducible, but in only one (9%) of the 11 patients in whom muscle contraction was not inducible (p < 0.01). No significant relationship was observed between pain control and various sensory symptoms, including the presence of hypesthesia, spontaneous dysesthesia, hyperpathia, and allodynia, or the disappearance of the N20 component of the median nerve—evoked somatosensory scalp potential. No significant relationship existed between the effect of MC stimulation on the pain and stimulation-induced phenomena, including paresthesia, improvement in motor performance, and attenuation of involuntary movements.
Conclusions. These findings suggest that the pain control afforded by MC stimulation requires neuronal circuits that are maintained by the presence of intact corticospinal tract neurons originating from the MC. Preoperative evaluation of motor weakness of the painful area appears to be useful for predicting a favorable response to MC stimulation in the control of poststroke pain.
Yoichi Katayama, Donald P. Becker, Toru Tamura and David A. Hovda
✓ An increase in extracellular K+ concentration ([K+]e) of the rat hippocampus following fluid-percussion concussive brain injury was demonstrated with microdialysis. The role of neuronal discharge was examined with in situ administration of 0.1 mM tetrodotoxin, a potent depressant of neuronal discharges, and of 0.5 to 20 mM cobalt, a blocker of Ca++ channels. While a small short-lasting [K+]e increase (1.40- to 2.15-fold) was observed after a mild insult, a more pronounced longer-lasting increase (4.28- to 5.90-fold) was induced without overt morphological damage as the severity of injury rose above a certain threshold (unconscious for 200 to 250 seconds). The small short-lasting increase was reduced with prior administration of tetrodotoxin but not with cobalt, indicating that neuronal discharges are the source of this increase. In contrast, the larger longer-lasting increase was resistant to tetrodotoxin and partially dependent on Ca++, suggesting that neurotransmitter release is involved. In order to test the hypothesis that the release of the excitatory amino acid neurotransmitter glutamate mediates this increase in [K+]e, the extracellular concentration of glutamate ([Glu]e) was measured along with [K+]e. The results indicate that a relatively specific increase in [Glu]e (as compared with other amino acids) was induced concomitantly with the increase in [K+]e. Furthermore, the in situ administration of 1 to 25 mM kynurenic acid, an excitatory amino acid antagonist, effectively attenuated the increase in [K+]e. A dose-response curve suggested that a maximum effect of kynurenic acid is obtained at a concentration that substantially blocks all receptor subtypes of excitatory amino acids. These data suggest that concussive brain injury causes a massive K+ flux which is likely to be related to an indiscriminate release of excitatory amino acids occurring immediately after brain injury.
Hideki Oshima, Yoichi Katayama and Teruyasu Hirayama
Object. The collateral vessels in moyamoya disease appear to retain their ability to constrict during hypocapnia but not to dilate during hypercapnia. It has been claimed that hypercapnia, as well as hypocapnia, decreases the blood flow in regions perfused by collateral vessels, presumably because of intracerebral steal. If this holds true, the decrease in blood flow may be proportional to the global hyperemia in the brain. To establish appropriate hemodynamic control during revascularization surgery, the authors monitored the jugular bulb oxygen saturation (SjO2) intraoperatively, a method that could sensitively detect global hyperemia.
Methods. A total of 17 patients, most of whom presented with transient ischemic attacks or fluctuating neurological deficits, underwent intraoperative monitoring of their SjO2 and end-tidal carbon dioxide (ETCO2) after a state of anesthesia had been induced with isoflurane (Group 1) or propofol (Group 2). In eight of these patients, the regional cerebral blood flow (rCBF) of the collateral vessel territory was also monitored by laser Doppler flowmetry during the period of cortical exposure, and a total of 113 data sets (averaged values during 2.5-minute intervals) was collected. There was fluctuation in the ETCO2 levels ranging from 36 to 44 mm Hg. The mean SjO2 level was clearly greater (p < 0.01) in Group 1 (71.8 ± 2.2%) than in Group 2 (63.3 ± 2.1%). An episodic fall in rCBF was observed in association with a transient increase in SjO2. Such an event was not uncommon in Group 1 and there was a greater risk of rCBF decreasing when SjO2 exceeded a cutoff level of 76% (p < 0.01). This level could sometimes be reached at a broad range of ETCO2 readings (37–44 mm Hg). In Group 2, similar events sometimes occurred when SjO2 increased beyond 70%. However, this level could be reached only with a higher ETCO2 (42–44 mm Hg). The rCBF level was negatively correlated to SjO2 (p < 0.01), but not always to ETCO2, indicating that the episodic fall in rCBF was closely related to global hyperemia rather than the absolute level of hypercapnia.
Conclusions. The observed association between a fall in rCBF and global hyperemia supports the intracerebral steal hypothesis and indicates that it is prudent to avoid excessive global hyperemia. The optimal range of CO2 for isoflurane is more restricted than that for propofol, presumably because isoflurane induces hyperemia by itself. Monitoring of SjO2 appears to represent the most practical technique for detecting global hyperemia as well as global ischemia, both of which may cause ischemic complications in moyamoya disease.
Experimental study in cats
Antonio A. F. DeSalles, Yoichi Katayama, Donald P. Becker and Ronald L. Hayes
✓ Cholinergic stimulation by microinjection of drugs into a region surrounding the lateral half of the brachium conjunctivum selectively produces a non-opiate form of pain suppression in the cat. Since this suppression does not appear to involve neural systems that mediate morphine analgesia, stimulation of this pontine parabrachial region (PBR) may potentially be useful for control of human pain resistant or tolerant to opiate treatment. Because of technical problems associated with the clinical use of microinjection techniques in the human brain, we investigated whether electrical stimulation of the PBR can produce pain suppression similar to pain suppression produced by cholinergic stimulation. The results indicate that electrical stimulation of an area generally corresponding to the PBR can also produce significant pain suppression. Although the PBR is a region previously implicated in a variety of behavioral and physiological functions, the stimulation parameters that produce maximal pain suppressive effects (namely, low frequency and relatively low intensity) were not associated with noticeable changes in such functions. The prolonged onset period and persistent analgesic effects outlasting the period of stimulation — features that have been reported in other studies of brain stimulation-produced pain suppression — were observed in the present study. The time course of pain suppression did not parallel other changes in behavioral and physiological functions. These data indicate that electrical stimulation of the PBR, under certain stimulation parameters, can activate previously demonstrated neural populations related to pain suppression without affecting neural elements contributing to other behavioral or physiological functions. The authors suggest that electrical stimulation of the PBR may be clinically applicable for treatment of human pain.
Naoyuki Hattori, Yoichi Katayama, Yoshio Maya and Alexander Gatherer
Object. Stereotactic evacuation of hematoma has been reported to reduce the incidence of mortality and to improve functional outcome in patients with spontaneous putaminal hemorrhage. Stereotactic evacuation of hematoma has not been widely accepted as a standard therapy, however, because its effect on functional outcome has been regarded as marginal and there have been no randomized trials with sufficient statistical power to quantify the benefits of this procedure. The authors reassessed the value of stereotactic evacuation of hematoma by analyzing its impact on activities of living during the chronic period following spontaneous putaminal hemorrhage in a randomized study.
Methods. Four hundred ninety patients were entered into the study. The severity of their hemorrhages was graded neurologically on admission (neurological grades: 1, eyes are open; 2, eyes are closed but open to weak stimuli; 3, eyes are closed but open to strong stimuli; 4, eyes do not open but extremities move to stimuli; and 5, eyes do not open and extremities do not move to stimuli). Patients with Grade 2 and those with Grade 3 were randomized into two groups with different treatment protocols (Group I, stereotactic evacuation of the hematoma; and Group II, conservative treatment). Patients assigned neurological Grade 4 or 5 were excluded from the study because a large-scale retrospective study in Japan revealed that surgical treatment in patients assigned to these neurological grades does not improve functional outcome. Among the 490 patients, 242 were randomized strictly. This patient population comprised 148 men and 94 women ranging in age from 38 to 80 years (mean 60.5 years).
Compared with Group II, Group I treatment resulted in a lower mortality rate and better recovery to functional independence in patients with neurological Grade 3. In patients with Grade 2, Group I treatment contributed to a better recovery of functional outcome and a lower mortality rate, but the difference was not significant. Multivariate analysis confirmed that stereotactic evacuation of the hematoma was contributory to a better recovery in functional outcome.
Conclusions. Stereotactic evacuation of hematoma is clearly of value in selected patients with spontaneous putuminal hemorrhage, whose eyes are closed but will open in response to strong stimuli (neurological Grade 3) on admission.
Yoichi Katayama, Toru Nakamura, Donald P. Becker and Ronald L. Hayes
✓ Intracranial pressure (ICP) was recorded continuously in chronically prepared, unanesthetized cats in order to investigate the effects on ICP of the cholinergic agonist, carbamylcholine (carbachol), injected by microsyringe needles into the dorsal pontine tegmentum. As reported previously, carbachol microinjections into the medial part of the cholinoceptive pontine inhibitory area (CPIA) located ventromedially to the locus coeruleus produced a comatose state characterized by a profound unresponsiveness to external stimuli, desynchronized electroencephalograms (EEG's), and suppression of postural somatomotor and sympathetic visceromotor functions. Four of six ICP records following carbachol microinjections into the CPIA showed small but significant increases which occurred in association with these carbachol effects. Tracings of ICP increases ranged up to 3.2 mm Hg and were similar in shape to plateau waves. The start and resolution of these carbachol-induced ICP variations were closely associated with the onset and termination of EEG desynchronization and signs of reduced cervical sympathetic tone, but not with changes in systemic arterial blood pressure or arterial pCO2. Temporal associations between ICP increases, desynchronized EEG's, and signs of reduced sympathetic tone were repeatedly confirmed during recovery periods associated both with recurrent comatose states following wakefulness produced by various intensities of external stimulation and with spontaneously occurring states resembling rapid eye movement sleep. The authors infer that carbachol-induced ICP variations may be produced by increased cerebral blood volume in response to accelerated cerebral metabolism and reduced vasoconstrictor tone of cervical sympathetic nerves. The simultaneous occurrence of continuously accelerated cerebral metabolism and reduced cervical sympathetic tone can neither be seen in physiologically normal, awake organisms nor produced by other known experimental manipulations of the central nervous system. Such a paradoxical relationship appears to be a unique consequence of activity within the CPIA. These data suggest that episodic activity within the CPIA may provide at least one endogenous neural basis for plateau waves seen during certain pathological conditions such as disturbed cerebrospinal fluid (CSF) absorption or with reduced equilibrium volume of CSF space.
Report of two cases
Takashi Tsubokawa, Yoichi Katayama and Takamitsu Yamamoto
✓ Persistent hemiballismus after stroke is often difficult to treat. The ballistic movement is sometimes so violent that progressive exhaustion results. The authors report two such cases, which were successfully treated by chronic thalamic stimulation. The lesions responsible for the ballistic movement in these patients were located near the subthalamic nucleus and in the putamen, respectively. The thalamic nucleus ventrolateralis and nucleus ventralis intermedius were stimulated with 0.2 to 0.3 msec pulses at 50 to 150 Hz and 4 to 7 V continuously during the day. Several weeks later, complete control of the hemiballismus was achieved during stimulation. The improvement was clearly not attributable to spontaneous recovery, because ballistic movement reappeared after termination of the stimulation. The stimulation has remained effective for more than 16 months in both cases without any serious complications. Chronic thalamic stimulation appears to be useful for controlling persistent hemiballismus, as it is for other involuntary movement disorders.