Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model.

Specific neuroprotective strategies to minimize cerebral damage caused by severe hypoxia or hypovolemia are lacking. Based on previous studies showing that relaxin-2/serelaxin increases cortical cerebral blood flow, we postulated that serelaxin might provide a neuroprotective effect. Therefore, we tested serelaxin in two emergency models: hypoxia was induced via inhalation of 5% oxygen and 95% nitrogen for 12 min; thereafter, the animals were reoxygenated. Hypovolemia was induced and maintained for 20 min by removal of 50% of the total blood volume; thereafter, the animals were retransfused. In each damage model, the serelaxin group received an intravenous injection of 30 µg/kg of serelaxin in saline, while control animals received saline only. Blood gases, shock index values, heart frequency, blood pressure, and renal blood flow showed almost no significant differences between control and treatment groups in both settings. However, serelaxin significantly blunted the increase of lactate during hypovolemia. Serelaxin treatment resulted in significantly elevated cortical cerebral blood flow (CBF) in both damage models, compared with the respective control groups. Measurements of the neuroproteins S100B and neuron-specific enolase in cerebrospinal fluid revealed a neuroprotective effect of serelaxin treatment in both hypoxic and hypovolemic animals, whereas in control animals, neuroproteins increased during the experiment. Western blotting showed the expression of relaxin receptors and indicated region-specific differences in relaxin receptor-mediated signaling in cortical and subcortical brain arterioles, respectively. Our findings support the hypothesis that serelaxin is a potential neuroprotectant during hypoxia and hypovolemia. Due to its preferential improvement of cortical CBF, serelaxin might reduce cognitive impairments associated with these emergencies.

A novel etiology for craniospinal hypovolemia: a case of inferior vena cava obstruction.

The authors report on a patient with craniospinal hypovolemia and inferior vena cava obstruction, and describe how the two conditions may be linked. This unique report further advances the emerging literature on spinal CSF venous fistulae.

[Neuro-otological Studies of Patients Suffering from Dizziness with Cerebrospinal Fluid Hypovolemia after Traffic Accident-associated Whiplash Injuries].

Vertigo and dizziness are common clinical manifestations after traffic accident-associated whiplash injury. Recently, Shinonaga et al. (2001) suggested that more than 80% of patients with whiplash injury complaining of these symptoms showed cerebrospinal (CSF) hypovolemia on radioisotope (RI) cisternography (111In-DTPA). However, neuro-otological studies to investigate the pathophysiological mechanisms underlying these symptoms have been insufficient. In the present study, patients complaining of these symptoms with CSF hypovolemia after traffic accidents were investigated with posturography and electronystagmography (ENG). Fourteen patients (4 men, 10 women; 24-52 yr) were examined with posturography and showed parameters (tracking distance & area) significantly (p<0.01) larger than those of healthy subjects. Among them, five cases (1 man, 4 women; 31-52 yr) were further investigated with ENG. The slow phase peak velocities of optokinetic nystagmus (OKN) and optokinetic-after nystagmus (OKAN) were significantly (p<0.01) reduced (62.64±6.9 SD deg/sec, 60.76±10.74 SD deg/sec, respectively) and frequencies of OKN were reduced (139.7±10.75 SD), while the ocular smooth pursuit was relatively preserved. Magnetic resonance images (sagittal view) of these five patients demonstrated the downward displacement of the cerebellar tonsils and flattening of the pons, which are characteristic features of CSF hypovolemia, called "brain sagging." Our results suggest that brain sagging due to CSF hypovolemia impairs vestibular and vestibulocerebellar functions, which may cause dizziness and vertigo.

Duret hemorrhage after lumbar drainage.

Lumbar drainage (LD) is considered as a simple and effective procedure for the treatment of intracerebral hemorrhage with ventricular involvement. However, cerebrospinal fluid overdrainage and hypovolemia due to LD could induce severe fatal complications, which include transtentorial herniation and infratentorial hemorrhage. Here, we describe a 63-year-old man with transtentorial herniations and Duret hemorrhage attributable to LD after the operation of thalamic hematoma removal. This is probably the first reported case of severe complications of LD. Thus, complications related to transtentorial herniations and Duret hemorrhage should be kept in mind while performing LD.

Case report: two cases of hearing impairment due to intracranial hypotension.

We report two cases of spontaneous intracranial hypotension (SIH) that presented with orthostatic hearing impairment. Pure tone audiometry in case 1 and distortion-produced otoacoustic emissions (DPOAEs) in case 2 clearly revealed orthostatic low-frequency hearing impairment. The symptoms resolved with conservative therapy in case 1, but they did not resolve completely after three treatments with epidural blood patch in case 2. The orthostatic changes at low-frequency that were present in both examinations indicated a relative endolymphatic hydrops due to SIH. Both otological examinations were useful to infer the pathophysiology of hearing impairment associated with SIH.

[Case of cerebrospinal fluid hypovolemia possibly due to acceleration of cerebrospinal fluid absorption].

The authors present a case of a 31-year-old man suffering from intractable cerebrospinal fluid hypovolemia (CSFH), in whom autologous epidural blood patch at the cervical, thoracolumbal, and sacral sites was not effective. Repeated radionuclide cisternography reproducibly demonstrated "early accumulation of radioactivity in the bladder", "cystic accumulation of radioactivity at the sacral site" and "less activity than expected over the cerebral convexities"; but computerized tomography myelography did not demonstrate CSF leakage but detected a sacral cyst. These repeated radionuclide cisternography findings suggested unusually rapid uptake of tracer by the circulation but did not always CSF leakage. The finding of strong accumulation of radioactivity in the sacral cyst might mean the opposite CSF flow against normal caudal-cranial flow. The formation of this abnormal cranial-caudal CSF flow could be produced with CSF leakage or abnormal absorption at the caudal site, where the cyst existed in the patient. Therefore, it is not unreasonable to suppose that the sacral cyst appeared to be responsible for development of CSFH in the patient. The possibility of acceleration of cerebrospinal fluid absorption in the sacral cyst was proposed for the cause of CSFH if CSF leakage was denied.

Subdural hematoma in spontaneous CSF hypovolemia.

Of 67 consecutive patients with spontaneous CSF hypovolemia (SCH), 11 (16.4%) had subdural hematoma (SDH). Patients with SDH were older (p = 0.005), more likely to be male (p = 0.035), and displayed longer time to diagnosis of SCH (p = 0.019) than those without SDH. All patients with SDH showed the findings of pseudo-subarachnoid hemorrhage on CT and responded favorably to epidural blood patches and neurosurgical drainage.

Herniation secondary to critical postcraniotomy cerebrospinal fluid hypovolemia.

OBJECTIVE: Cerebrospinal fluid hypovolemia resulting in postural headaches is a well-known clinical entity, but severe forms of cerebrospinal fluid hypovolemia with altered mental status and signs of transtentorial herniation ("brain sag") have rarely been reported. This article describes the clinical features of brain sag after craniotomy in an attempt to increase recognition of this syndrome. METHODS: Between April 2001 and January 2003, 220 consecutive patients with subarachnoid hemorrhage were prospectively enrolled in the Columbia Subarachnoid Hemorrhage Outcomes Project; 137 underwent craniotomy for aneurysm clipping. Among these patients, the diagnosis of brain sag was made when all three of the following criteria were present: clinical signs of transtentorial herniation, head computed tomographic scans revealing effacement of the basal cisterns with an oblong brainstem, and improvement of symptoms after placement of the patient in the Trendelenburg position (-15 to -30 degrees). For each patient, the symptoms, clinical course, and subsequent response to treatment were characterized. In addition, brainstem dimensions were measured on computed tomographic scans taken before, during, and after resolution of brain sag. A "sag ratio" was generated for these time points by dividing the maximum anteroposterior distance by the maximum bipeduncular distance. RESULTS: Eleven (8.0%) of 137 aneurysmal subarachnoid hemorrhage patients treated by craniotomy and an intraoperative spinal drain met the criteria for brain sag. Signs of transtentorial herniation developed most commonly between 2 and 4 days postoperatively. Pupillary asymmetry was noted in 10 (91.0%) of 11 patients, whereas the other patient demonstrated extensor posturing. The Trendelenburg position reversed the symptoms in all patients. The mean sag ratios before, during, and after resolution of brain sag were 0.91 +/- 0.03 (mean +/- standard error), 1.18 +/- 0.03, and 0.91 +/- 0.03, respectively. This represented a 30.9% elongation of the brainstem during sag (P < 0.001) and a 23.6% change back to baseline after resolution of the syndrome (P < 0.002). There was no significant difference between the presag and postsag ratios. CONCLUSION: Severe cerebrospinal fluid hypovolemia after craniotomy may produce a dramatic herniation syndrome that is completely reversed by the Trendelenburg position. Brain sag should be included in the differential diagnosis for acute postoperative clinical deterioration in this patient population.

Broadening the clinical spectrum: unusual presentation of spontaneous cerebrospinal fluid hypovolemia. Case report.

The syndrome of spontaneous intracranial hypotension is characterized by orthostatic headaches in conjunction with reduced cerebrospinal fluid (CSF) pressure or CSF volume, and characteristic magnetic resonance (MR) imaging findings. A 50-year-old man presented with a 1-year history of paroxysmal ataxia of gait and short attacks of blurred vision when he stood up from a recumbent position and began to walk. Orthostatic headache was not a feature of his clinical presentation. Magnetic resonance images of the brain revealed diffuse enhancement of the dura mater and hygromas over both cerebral convexities. Magnetic resonance images of the spine demonstrated dilated cervical epidural veins and dilation of the perimedullary veins. Radionuclide cisternography identified a CSF leakage that was localized to the T12-L1 level on subsequent myelograms and on computerized tomography scans obtained after the myelograms. An epidural blood patch was administered and visualized with tungsten powder. The patient's clinical symptoms and sites of disease on imaging completely resolved. The unusual clinical presentation in this case--paroxysmal ataxia of gait, lack of orthostatic headaches, and dilated epidural and perimedullary venous plexus--supports a recently noted broadening of both the clinical and imaging characteristics of spontaneous intracranial hypovolemia.

Syndrome of cerebral spinal fluid hypovolemia: clinical and imaging features and outcome.

OBJECTIVE: To investigate clinical, MRI, and radioisotope findings and therapeutic outcome of the syndrome of CSF hypovolemia. METHODS: Retrospective review was performed of 30 consecutive patients (10 men, 20 women; mean age 37 years) with the syndrome of CSF hypovolemia. RESULTS: All patients had an orthostatic headache, which was alleviated to a variable extent on recumbency. Additional clinical symptoms included nausea, dizziness, neck stiffness, blurring of vision, tinnitus, plugged ear, hearing difficulties and radicular pain of the arm. Eighty-two percent of the patients had CSF opening pressure less than 60 mm H2O, 59% had CSF pleocytosis, and 95% had increased CSF protein. Brain MRI showed diffuse pachymeningeal gadolinium enhancement on T1-weighted image in 83%, which was seen as hyperintense signals on T2-weighted imaging. Other features included subdural hematoma/hygroma in 17% and descent of the brain in 48% of the patients. Radioisotope cisternographic results identified CSF leakage sites in 52%, most often at the lumbar region. Also observed were limited ascent of the tracer to the cerebral convexity (91%), early appearance of radioisotope in the bladder (65%), and early soft tissue uptake of radioisotope (43%). Epidural blood patches were performed in 23 patients, which produced complete resolution of headaches in 70%. Two patients underwent drainage of subdural hematoma. None died or were disabled during hospitalization. CONCLUSIONS: Patients with CSF hypovolemia frequently have distinct MRI and radioisotope cisternographic abnormalities and often respond favorably to an epidural blood patch.