Electroclinical phenotype in Rubinstein-Taybi syndrome.

OBJECTIVE: Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder (1:125.000) characterized by growth retardation, psychomotor developmental delay, microcephaly and dysmorphic features. In 25% of patients seizures have been described, and in about 66% a wide range of EEG abnormalities, but studies on neurological features are scant and dated. The aim of this study is to describe the electroclinical phenotype of twenty-three patients with RSTS, and to try to correlate electroclinical features with neuroradiological, cognitive and genetic features. PATIENTS AND METHODS: Electroclinical features of twenty-three patients with RSTS (age between18months and 20years) were analyzed. Sleep and awake EEG was performed in twenty-one patients, and brain MRI in nineteen patients. All subjects received cognitive evaluation. RESULTS: EEG abnormalities were observed in 76% (16/21) of patients. A peculiar pattern prevalent in sleep, characterized by slow monomorphic activity on posterior regions was also observed in 33% (7/21) of patients. Almost no patient presented seizures. Eighty-four percentage of patients had brain MRI abnormalities, involving corpus callosum and/or posterior periventricular white matter. Average General Quotient (GQ) was 52, while average IQ was 55, corresponding to mild Intellectual Disability. The homogeneous electroclinical pattern was observed mainly in patients with more severe neuroradiologic findings and moderate Intellectual Disability/Developmental Disability (ID/DD). No genotype-phenotype correlations were found. CONCLUSION: The specific electroclinical and neuroradiological features described may be part of a characteristic RSTS phenotype. Wider and longitudinal studies are needed to verify its significance and impact on diagnosis, prognosis and clinical management of RSTS patients.

Refractory intracranial hypertension and "second-tier" therapies in traumatic brain injury.

OBJECTIVE: To quantify the occurrence of high intracranial pressure (HICP) refractory to conventional medical therapy after traumatic brain injury (TBI) and to describe the use of more aggressive therapies (profound hyperventilation, barbiturates, decompressive craniectomy). DESIGN: Prospective study of 407 consecutive TBI patients SETTING: Three neurosurgical intensive care units (ICU). MEASUREMENTS AND RESULTS: Intracranial pressure (ICP) was studied during the first week after TBI; 153 patients had at least 1 day of ICP>20 mmHg. Early surgery was necessary for 221 cases, and standard medical therapy [sedation, mannitol, cerebrospinal fluid (CSF) withdrawal, PaCO2 30-35 mmHg] was used in 135 patients. Reinforced treatment (PaCO2 25-29 mmHg, induced arterial hypertension, muscle relaxants) was used in 179 cases (44%), and second-tier therapies in 80 (20%). Surgical decompression and/or barbiturates were used in 28 of 407 cases (7%). Six-month outcome was recorded in 367 cases using the Glasgow outcome scale (GOS). The outcome was favorable (good recovery or moderate disability) in 195 cases (53%) and unfavorable (all the other categories) in 172 (47%). HICP was associated with worse outcome. Outcome for cases who had received second-tier therapies was significantly worse (43% favorable at 6 months, p=0.03). CONCLUSIONS: HICP is frequent and is associated with worse outcome. ICP was controlled by early surgery and first-tier therapies in the majority of cases. Profound hyperventilation, surgical decompression and barbiturates were used in various combinations in a minority of cases. The indications for surgical decompression and/or barbiturates seem restricted to less than 10% of severe TBI.

Oxygen and carbon dioxide in the cerebral circulation during progression to brain death.

BACKGROUND: The authors propose that for a moderate reduction of perfusion during progressive irreversible ischemia, oxygen extraction increases to maintain aerobic metabolism, and arteriojugular oxygen difference (AJDo2) increases. Because of reduced carbon dioxide washout, venoarterial difference in carbon dioxide tension (DPco2) increases, with no change in the DPco2/AJDo2 ratio. With further reduction of cerebral perfusion, the aerobic metabolism will begin to decrease, AJDo2 will decrease while DPco2 will continue to increase, and the ratio will increase. When brain infarction develops, the metabolism will be abated, no oxygen will be consumed, and no carbon dioxide will be produced. METHODS: The authors studied 12 patients with acute cerebral damage that evolved to brain death and collected intermittent arterial and jugular blood samples. RESULTS: Four patterns were observed: (1) AJDo2 of 4.1 +/- 0.7 vol%, DPco2 of 6.5 +/- 1.9 mmHg, and a ratio of 1.55 +/- 0.3 with cerebral perfusion pressure of 62.5 +/- 13.4 mmHg; (2) a coupled increase of AJDo2 (5.8 +/- 0.7 vol%) and DPco2 (10.1 +/- 1.0 mmHg) with no change in ratio (1.92 +/- 0.14) and cerebral perfusion pressure (57.9 +/- 5.8 mmHg); (3) AJDo2 of 4.7 +/- 0.4 vol% with an increase in DPco2 (11.8 +/- 1 mmHg) and correspondingly higher ratio (2.7 +/- 0.2); in this phase, cerebral perfusion pressure was 39.7 +/- 10.5 mmHg; (4) immediately before diagnosis of brain death (cerebral perfusion pressure, 17 +/- 10.4 mmHg), there was a decrease of AJDo2 (1.1 +/- 0.1 vol%) and of DPco2 (5.3 +/- 0.6 mmHg) with a further ratio increase (5.1 +/- 0.8). CONCLUSIONS: Until compensatory mechanisms are effective, AJDo2 and DPco2 remain coupled. However, when the brain's ability to compensate for reduced oxygen delivery is exceeded, the ratio of DPco2 to AJDo2 starts to increase.

Inaccurate early assessment of neurological severity in head injury.

Intubation, which requires sedation and myorelaxants, may lead to inaccurate neurological evaluation of severely head-injured patients. Aims of this study were to describe the early clinical evolution of traumatic brain injured (TBI) patients admitted to intensive care unit (ICU), to identify cases of over-estimated neurological severity, and to quantify the risk factors for this over-estimation. A total of 753 TBI patients consecutively admitted to ICU of three academic neurosurgical hospitals (NSH) were assessed. Cases whose severity was potentially over-estimated were identified by four criteria and indicated as "mistakenly severe" (MS): (1) no surgical intracranial masses; (2) could not follow commands at neurological assessment; (3) were dismissed from the ICU in < or =3 days to a regular ward; and (4) had regained the ability to obey commands. A total of 675 patients were intubated and/or sedated-paralyzed at the post-stabilization evaluation. In all, 304 patients had surgically treated intracranial masses. Among the 449 non-surgical cases, 58 patients fulfilling the criteria for MS were identified. The main features distinguishing MS from truly severe cases were younger age, higher Glasgow Coma Scale (GCS) score at all time points, Marshall classification of Computerized Tomographic (CT) scan mostly Diffuse Injury I and II, fewer pupillary abnormalities, and a lower frequency of hypoxia, hypotension, and extra-cranial injuries. In a certain proportion of non-surgical TBI patients, mostly intubated and sedated, neurological examination is difficult and severity can be over-estimated. Risk factors for this inaccurate evaluation can be identified, and clinical decisions should be based on further examination.

Arterio-jugular difference of oxygen content and outcome after head injury.

This study investigated AJDO2 (arterio-jugular difference of oxygen content) in a large sample of severely head-injured patients to identify its pattern during the first days after injury and to describe the relationship of AJDO2 with acute neurological severity and with outcome 6 mo after trauma. In 229 comatose head-injured patients, we monitored intracranial pressure, cerebral perfusion pressure, and AJDO2. Outcome was defined 6 mo after injury. Jugular hemoglobin oxygen saturation (SjO2) averaged 68%. The mean AJDO2 was 4.24 vol% (SD, 1.3 vol%). There were 80 measurements (4.6%) with SjO2 <55% and 304 (17.6%) with saturation >75%. AJDO2 was higher than 8.7 vol% in 8 measurements (0.4%) and was lower than 3.9 vol% in 718 (42%) measurements. AJDO2 was higher during the first tests and decreased steadily over the next few days. Cases with a favorable outcome had a higher mean AJDO2 (4.3 vol%; SD, 0.3 vol%) than patients with severe disability or vegetative status (3.8 vol%; SD, 1.3 vol%) and patients who died (3.6 vol%; SD, 1 vol%). This difference was significant (P < 0.001). We conclude that low levels of AJDO2 are correlated with a poor prognosis, whereas normal or high levels of AJDO2 are predictive of better results.

Intra-abdominal pressure may be decreased non-invasively by continuous negative extra-abdominal pressure (NEXAP).

OBJECTIVE: To investigate the possibility of artificially decreasing intra-abdominal pressure (IAP) by applying continuous negative pressure around the abdomen. MATERIAL AND METHODS: We investigated the effects of negative extra-abdominal pressure (NEXAP) on IAP and central venous pressure (CVP) in 30 patients admitted to our intensive care unit (age 57+/-17 years, BMI 26.1+/-4.0 kg/m2, SAPS II 41.8+/-17.0). Patients with severe hemodynamic instability and/or those admitted following a laparotomy were not studied. Measurements included bladder pressure as an estimate of IAP, CVP, invasive mean arterial pressure (MAP) and heart rate (HR). In five patients extensive hemodynamic measurements were also taken using a Swan-Ganz catheter. Following measurements at baseline (Basal), NEXAP (Life Care - Nev 100, Respironics) was applied on the abdomen, in random order, at a pressure equal to IAP (NEXAP0), 5 cmH(2)O (NEXAP-5) or 10 cmH(2)O (NEXAP-10) more negative than NEXAP0. RESULTS: Basal IAP ranged from 4 to 22 mmHg. NEXAP decreased IAP from 8.7+/-4.3 mmHg to 6+/-4.2 (Basal vs NEXAP0 p<0.001). There was a further decrease of IAP when more negative pressure was applied: 4.3+/-3.2 mmHg, 3.8+/-3.7 mmHg (NEXAP-5 and NEXAP-10 vs NEXAP0, respectively, p<0.001). Similarly, CVP decreased from 9.3+/-3.4 mmHg to 7.5+/-3.8 (Basal vs NEXAP-10, p<0.001). The lower the IAP when NEXAP was applied, the lower the CVP (r2=0.778, p<0.001, multiple linear regression). When measured, cardiac output did not significantly change with NEXAP. CONCLUSIONS: Negative extra-abdominal pressure may be applied in critically ill patients to decrease intra-abdominal pressure non-invasively.