Although whiplash-associated disorder (WAD) is usually self-limited, with a good prognosis (1), some patients suffer persistent and intractable symptoms. Most patients with chronic WAD show no objective neurological deficits, but complain of symptoms such as headache, dizziness, memory loss, and nausea (2). Patients with WAD are classified according to the Quebec criteria, which indicate the course of treatment (1). However, few data are available regarding the pathogenesis, management, and prognosis of chronic WAD (3,4). Many treatments have proven to be unsatisfactory. For example, Lord et al. (5) reported that radiofrequency denervation of facet joints may be effective in cervicogenic headache after an automobile accident, but Stovner et al. (6) reported that the procedure is probably not beneficial in cervicogenic headache.
Patients with cerebrospinal fluid (CSF) leak experience miscellaneous symptoms similar to those of chronic WAD. Acute CSF leak occurs most frequently after lumbar puncture (postdural puncture headache: PDPH). Chronic CSF leak in the absence of dural puncture can lead to the syndrome of intracranial hypotension (IH) (7–10). The cardinal manifestation of IH is orthostatic headache, often accompanied by nausea, visual impairment, hearing loss, or neck stiffness (11,12).
Methods for diagnosis of IH have improved recently. Magnetic resonance imaging (MRI) typically reveals diffuse pachymeningeal enhancement, frequently in association with sagging of the brain, tonsillar descent, and posterior fossa crowding (13–15). By radioisotope (RI) cisternography, accumulation of radioactivity outside the subarachnoid space and failure of the tracer to reach the convexities of the brain provide an indication of a CSF leak (16–18). Rapid disappearance of RI from the subarachnoid space and early appearance in the urinary bladder also suggest a leak of CSF and its early reuptake into the venous system (9). IH may be primary (related to an occult dural leak, i.e., spontaneous IH) or secondary to conditions, such as trauma (spinal injury, head injury), surgery (pneumonectomy, craniotomy, spinal surgery), or systemic disease (diabetic coma, uremia) (19). Proposed etiologies include rupture of a congenital subarachnoid cyst or rupture of a diverticulum of the spinal nerve root sleeve resulting in traumatic tear of the nerve root sleeve (19–21).
Progress with respect to diagnostic methods and increased understanding of the etiology of IH has shed light on potential therapies. Placement of an epidural blood patch (EBP) is an effective treatment for PDPH. Although conservative measures are often undertaken first, EBP is the treatment of choice for IH (7–10). We hypothesized that in some cases of chronic WAD with intractable symptoms, CSF leak may be involved and that EBP could be an effective therapy for chronic WAD. Therefore, we investigated the relation between chronic WAD and CSF leak by RI cisternography and evaluated whether EBP is effective in the treatment of chronic WAD.
Institutional and ethics committee approval were obtained for this study, and all participants provided written informed consent. During the years 2002–2004, 124 consecutive patients suffering from intractable and often disabling symptoms were referred to our departments with suspected WAD. Subjects in this study were patients with chronic WAD, without fracture or dislocation, but with symptoms lasting longer than 3 mo. Our criteria for chronic WAD included at least two of the following: headache, cervical pain, dizziness, nausea, visual impairment, auditory symptoms, and memory loss. Of the 124 patients, 10 given an EBP at another hospital, 1 with dislocation of the cervical spine, 7 with a history of spinal surgery, and 40 without an obvious accident before onset were excluded from this study (Fig. 1). Thus, subjects were 66 patients with chronic WAD. Backgrounds were obtained, and symptoms were recorded.
After an observation period of 2 wk, participants underwent RI cisternography to determine the presence of CSF leak. Details of the RI cisternography were as described previously (22). Thirty-seven MBq 111In-diethylene triamine pentaacetic acid in 1 mL solution was injected with the patient in the lateral position via lumbar puncture with a 25-G pencil-point spinal needle. Whole-neural axis images were obtained 2.5, 6, and 24 h after injection. The CSF space was scanned downward from the head at a speed of 5 cm per min. RI cisternography results were recorded and analyzed. Radioactivity located beyond the dural border was considered a direct indicator of CSF leak. Radioactivity in the urinary bladder within 2.5 h after injection was considered an indirect indicator of CSF leak (early accumulation in the bladder).
In patients with an identified CSF leak, conventional therapies such as bed rest, infusion of lactated Ringer’s solution, and some analgesics were tried. If these therapies were not effective, EBP placement was scheduled. The EBP was performed at the region of the leak by RI finding and in the lumbar region in the case of only early bladder accumulation. Patients were not premedicated and were not sedated during EBP administration. With the patient in the prone position, the epidural space was identified via a median approach by loss of resistance to saline. An 18-G Touhy needle was inserted under fluoroscopic guidance to keep the tip of needle midline of the spinal canal in the epidural space. Autologous blood was obtained aseptically, and a 40-mL solution was made from 30 mL autologous blood and 10 mL contrast medium (iotrolan, 240 mg I/mL). Under fluoroscopic observation, 20 mL of this solution was slowly injected into the epidural space through the Tuohy needle at a rate of approximately 0.5 mL/s, unless the patient complained of pain. If the patient complained of low back pain or radiculopathy, injection was terminated and anterior–posterior and lateral epidurograms were obtained. If the initial injection of 20 mL solution could not cover the suspected site of CSF leak (CSF emerging from multiple intervertebral foramina by RI cisternography), an additional solution was slowly injected until coverage of the suspected CSF leak site, or until the patient’s complaint of pain, or until 20 mL injection. After injection, epidurograms were obtained. If symptoms did not improve within 1 mo of the procedures, additional EBPs were applied up to a total of three.
Symptoms were assessed upon referral, before placement of the first EBP (after an observation period), and 1 wk and 6 mo after placement of the first EBP with a self-assessment questionnaire. The clinical response was evaluated as follows: excellent, marked improvement and a return to normal routines; good, significant improvement but still disabled; poor, minimal or no improvement; worse, worse than before treatment. Responses of “excellent or good,” were assessed as improved. Responses of “poor or worse” were assessed as unimproved. The percentage of patients reporting each response was calculated. With respect to headache, a visual analog scale was used with 0 meaning no pain and 10 meaning the worst pain imaginable.
Work status was also evaluated (full-time work, part-time work, or sick leave) at our first referral and 6 mo after initial EBP. Follow-up RI cisternography was routinely recommended and assessed quantitatively by visual inspection (22).
Values are expressed as mean ± sd, unless otherwise indicated. Statistical analysis was performed by unpaired t-test, Fisher’s exact test, or Wilcoxon’s signed rank test. Statistical significance was set at P < 0.05. All statistical analyses were performed with commercially available software (StatView, version 5.0 for Windows; SAS Institute, Cary, NC).
Patient characteristics are shown in Table 1. Motor-vehicle accident was the most common cause of WAD. The mean duration of symptoms was 33 ± 38 mo. RI cisternography revealed a CSF leak in 37 of the 66 patients (56%). Early bladder accumulation was observed in all 37 patients. Direct RI leak was identified in 32 patients (Fig. 2). CSF leak was diagnosed in five patients in whom the site of the leak was unidentified, on the basis of early bladder accumulation and accelerated RI clearance. The most common site of CSF leak was the lumbar region (n = 18) (Fig. 3). With the exception of one patient, 36 patients with CSF leak were given an EBP because symptoms did not respond to conventional therapy.
Before placement of an EBP, headache (100% of patients, including orthostatic headache: 89%), memory loss (89%), dizziness (83%), visual impairment (81%), cervical pain (81%), nausea (78%), and auditory symptoms (53%) were reported. None of the patients had definite neurological deficits. Conventional therapies during a 2-week observation period did not change symptoms. One week after placement of the EBP, these symptoms were decreased significantly (P < 0.01), and the effects were also observed at the 6-mo follow-up examination (P < 0.01) (Fig. 4). Headache was the most improved symptom, followed by memory loss and visual impairment. As for headache visual analog scale scores, before EBP and follow-up EBP, were 8.8 ± 0.9 and 3.1 ± 1.9, respectively (P < 0.01).
The mean number of EBPs was 2.2 ± 0.7 per patient, and the mean injected volume was 37 ± 7.5 mL per injection. Although low back pain persisted for a few days in some patients, no serious complication, such as epidural abscess or spinal compression, was noted, even at the final follow-up examination. Two patients (5.6%) showed no symptomatic relief despite RI cisternographic improvement. Another two patients (5.6%) showed no symptomatic or radiological improvement.
A follow-up RI cisternography was performed in 25 patients and RI findings showed improvement of the CSF leak except for one patient. EBP therapy improved the work status in 32 of 36 patients (89%) (Fig. 5). None of the patients was working full-time before EBP administration, whereas 20 (56%) patients returned to full-time work with some residual symptoms after EBP therapy. Of the 20 patients who returned to full-time work, 12 underwent follow-up RI cisternography, which showed improvement of the CSF leak (Fig. 2).
We showed that CSF leak was improved in response to EBP therapy in some patients with chronic WAD and that symptoms associated with CSF leak improved significantly. These results indicate that the EBP is an effective treatment for chronic WAD involving CSF leak.
Some patients with whiplash experience persistent, intractable pain, and little is known regarding the etiology of chronic WAD (23). Patients with chronic WAD often experience neck pain, paresthesia, lower back pain, headache, dizziness, auditory symptoms, dysphasia, and visual symptoms (2). Some etiologies, such as cervical sympathetic overstrain (24), oculocephalic sympathetic dysfunction (25), and changes in central pain processing mechanisms (26), have been proposed. However, conventional treatments rarely resulted in a good response and manifestations are rarely revealed by routine computed tomography or MRI. Most of our patients had undergone MRI studies before our referral and had received no diagnosis of dysfunction. Many of these patients are labeled as having “litigation neurosis.” However, headaches may persist for years after litigation settlement (2).
IH has been recognized and established as a distinct clinical entity. Clinical manifestations of IH include headache, nausea, diplopia, auditory disorder, neck pain, visual field defect, and dizziness (11). Many of the symptoms of chronic WAD are similar to those of CSF leak. Some reports have determined the etiology of IH to be spinal CSF leak (26–28) and have suggested that trivial trauma can cause CSF leak. We reported the cases of two Barré–Liéou syndrome patients with spinal CSF leak that improved with EBP therapy (29). Barré–Liéou syndrome, which includes a group of symptoms such as headache, vertigo, tinnitus, and ocular problems, was initially described in 1926. Since then, similar symptoms have been observed in patients with injury in traffic accidents and attention has been focused on this relationship (30).
Our results clearly show that CSF leak can be an etiology of chronic WAD. The Quebec criteria categorize patients with WAD into five grades according to subjective symptoms and objective signs (1). According to this classification scheme, WAD patients without dislocation or fracture of the cervical spine are recommended for early rehabilitation and a return to work within 12 wk after the accident, whether headache, dizziness, memory loss, or nausea persist. Bed rest and adequate hydration are effective treatments for CSF leak, and early rehabilitation may worsen CSF leak. For patients in whom symptoms remain, further examination regarding CSF leak should be performed, and EBP should be the treatment of choice if CSF leak is observed.
RI cisternography is important in the identification of CSF leak, provides evidence for symptoms after an accident, and is useful in the assessment of the effect of EBP. In the present study, the majority of CSF leaks in patients with chronic WAD were found in the thoracolumbar region. We did not determine the reason why the thoracolumbar region is a target in chronic WAD. However, root sleeves in this region may tear easily in response to whiplash injury. Multiple root sleeves over a broad range may be involved.
EBP with fluoroscopic guidance has several advantages. Epidurography is simpler than MRI for checking the EBP spread and is also very useful for identifying individual variations in the EBP spread. In the present study, the spread pattern varied among patients, and it was difficult to predict cephalad, caudal, or unilateral spread. We also reported individual differences in contrast medium spread in the epidural space (31).
Two mechanisms have been proposed for the effectiveness of the EBP (32–34). The initial mechanism is that the transmitted pressure from the epidural injection (a tamponade effect) causes an increase in intracranial pressure that restores the brain to its normal position. The other possibility is that epidurally injected blood seals the dural defect and normal CSF production. In the present study, epidurography with a mixture of blood and contrast medium made it possible to visualize the extent and pattern of the spread in the epidural space. This method can be used to judge EBP spread and to minimize the volume of blood injected into the epidural space to cover all possible sites of CSF leak by RI cisternographic finding. Frequent EBP can cause epidural adhesion, spinal nerve damage, and other complications, including inadvertent dural puncture (35). Thus, the frequency of EBP injections should be limited. In patients requiring several EBP injections, the spread of the first patch can be identified epidurographically, allowing for easy identification of the area not covered. The level of needle insertion is particularly important in patients with IH because the sites of leakage are obscure in these patients compared to patients with PDPH (36,37). Thus, we performed EBP with fluoroscopy.
Crawford (38,39) reported a 70% success rate for EBP with 6–15 mL of blood in patients with PDPH. The success rate increased to 98% when the volume of blood was increased to 20 mL. However, the success rate of EBP in patients with IH is considerably less than that in patients with PDPH (30% vs 70%–90%) (40). Patients with spontaneous or traumatic IH often require more than one EBP, with some requiring up to six EBPs for lasting relief (37). In patients with PDPH, the CSF usually leaks from a single dural point, and this point is easy to identify. In contrast, the exact site of CSF leak is not easily identified in many cases of IH (37) and chronic WAD. Thus, to repair the CSF leak, the EBP spread must be more extensive in patients with chronic WAD than in those with PDPH. Another important difference between IH and PDPH is that leakage occurs from the anterior spinal canal in IH and from the posterior spinal canal in PDPH. The root sleeve is subject to dural tear in both spontaneous and traumatic IH because dural tissue is fragile at this location (41). The root sleeve is in the anterior spinal canal; EBP injected into the posterior epidural space should surround the spinal canal. Patients in our study were placed in the prone position, allowing for autologous blood to move to the anterior spinal canal by gravity, which was confirmed by fluoroscopy.
There are some limitations to this study. There was no control group in this study. However, patients received conventional therapies for longer than 3 mo before EBP, which did not improve their symptoms. Patients also received a 2 wk observation interval. We considered this period to be the control period, because symptoms were improved significantly immediately after EBP and this effect continued for at least 6 mo. In addition, the consecutive patients in this study were recruited for the possibility of CSF leak after a whiplash injury, so selection bias may have occurred. Thus, the rate of CSF leak in patients with chronic WAD may be less than our results indicate.
We were not able to determine the etiology for all of the patients in this study. Of the 66 patients with chronic WAD, 29 (44%) showed no CSF leak by RI cisternography. Thus, approximately half of these patients had other etiologies. We noted that symptoms associated with CSF leak, such as headache, visual impairment, and nausea, were improved dramatically after EBP therapy. However, some symptoms, such as cervical pain and dizziness, were not improved as much, indicating that some symptoms of chronic WAD may not be related to CSF leak. Indeed, in some patients, neck pain was improved by zygapophysial joint denervation performed after the present study. Further investigation will be necessary to determine the causes of these other symptoms.
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