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Venous Malformations Associated with Central Pain: Report of a Case

Cohen, Steven P., MD*‡,; Abdi, Salahadin, MD, PhD

doi: 10.1097/00000539-200211000-00048
TECHNOLOGY, COMPUTING, AND SIMULATION: Case Report
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*Department of Anesthesiology, Pain Management Center, Walter Reed Army Medical Center, Washington, DC, and Uniformed Services University of the Health Sciences, Bethesda, Maryland; †Department of Anesthesia and Critical Care, MGH Pain Center, Massachusetts General Hospital, Harvard Medical School, Boston; and ‡Department of Anesthesiology, New York University School of Medicine, New York, New York

July 26, 2002.

Address correspondence and reprint requests to Steven P. Cohen, MD, Department of Anesthesiology, New York University School of Medicine, 550 First Avenue, New York, NY 10016. Address e-mail to steven.cohen@med.nyu.edu.

Central pain (CP) results from lesions in the central nervous system (CNS) leading to damage to pathways involved in pain transmission. First described in 1883 (1), central lesions are frequently overlooked as a source of pain. One reason for this is a pervasive lack of knowledge among physicians regarding its characteristics. Yet, this syndrome is not uncommon. It affects approximately 8% of stroke patients, 10% of people with Parkinson’s disease, and more than 50% of people with spinal cord injuries (2). We report a patient with left-sided body pain strongly suggestive of CP who was noted to have extensive venous malformations on a magnetic resonance image (MRI) of her brain. This association has never been reported. The patient was treated with a variety of different medications, including the N-methyl-d-aspartate (NMDA) receptor antagonist dextromethorphan, which reduced her pain. Whereas the NMDA antagonist ketamine has been reported to relieve CP, in the only study evaluating dextromethorphan, the drug was found to have no benefit (3).

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Case Report

The patient was a 53-yr-old military dependent woman with a medical history significant for sarcoidosis and migraine headaches who was referred to the Walter Reed Army Medical Center Pain Clinic for a 2-yr history of continuous pain on the left side of her body that had become progressively worse over the past 6 wk. Over the previous 3 mo, she had also developed nonmigrainous headaches. She described her body pain as burning, knifelike, and exacerbated by stress and cold, damp weather. She also noted that her left foot and hand were sometimes colder than the right ones.

The patient’s medications were oxycodone with acetaminophen (Percocet), which reduced her pain somewhat, and lorazepam for sleep. She also reported previous pain relief with prednisone that had been prescribed in the past for sarcoidosis. Her physical examination revealed patchy areas of tactile hypesthesia and loss of thermal sensation but no hyperalgesia, allodynia, or focal neurologic deficits. On a visual analog scale (VAS) of 0–10, she rated her pain as a 9.

We believed the patient’s symptoms to be consistent with CP secondary to sarcoidosis and started her on amitriptyline, which was quickly changed to desipramine after she developed side effects. Aside from the aforementioned findings on her physical examination, subsequent neurology and psychiatry work-ups were negative. A gadolinium-enhanced MRI of her brain revealed central venous engorgement, consistent with giant hemangiomas, extending from the fronto-parietal cortex into the floor of the lateral ventricle and roof of the thalamus, larger on the right than the left (Figs. 1 and 2). No evidence of CNS sarcoidosis was detected. Given her MRI findings, we thought it likely that the venous malformations were responsible for the patient’s symptoms. Consequently, we referred her to a neurosurgeon who felt she was not a candidate for surgery.

Figure 1

Figure 1

Figure 2

Figure 2

At her next visit, the patient reported the desipramine to be ineffective. We then prescribed her the noncompetitive NMDA receptor antagonist dextromethorphan 60 mg per os tid, which resulted in moderate relief of her pain (VAS decreased from 9 to 6 of 10). Over the next several months, she was tried on clonidine, mexiletine, rofecoxib, and gabapentin. With the exception of gabapentin, which provided her with mild relief, these other drugs were ineffective. Four months after presenting to our clinic, the patient noted a burning pain starting intermittently on the right side of her body. At this point, we increased her dextromethorphan to 90 mg per os tid and started her on a sustained-release form of oxycodone in lieu of Percocet. With these adjustments, the patient reported a further improvement in symptoms (VAS decreased from 6 to 4). Two months later, she was transferred to an overseas duty assignment. A telephone follow-up 6 mo after her last visit revealed her average VAS score to be 3.

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Discussion

Because of its severity, incessant nature, and resistance to treatment, CP is one of the most devastating conditions known to humans. Patients typically describe an aching, burning pain on the contralateral side of a CNS lesion, exacerbated by cold, fear, or anxiety. This, as well as frequently encountered signs of autonomic dysfunction, have led some to postulate sympathetic mechanisms as playing a role in the disorder (4). On physical examination, sensory deficits, allodynia, or hyperalgesia may be present.

Virtually any condition affecting the CNS can lead to CP, particularly if the lesion involves part of the spinothalamic tract or thalamocortical projections. After detailed studies of neurosurgical interventions, Cassinari and Pagni (5) suggested that interruption of spinothalamocortical nociceptive pathways is the single most common abnormality seen with CP. Whereas the pathophysiology remains poorly understood, several hypotheses have been put forth to explain the phenomenon. These include disinhibition of nociceptive input (6), sympathetic dysfunction (4), denervation supersensitivity (7), and cellular mechanisms (8).

Glutamate and the NMDA receptor have been shown to play a role in CP (9). In clinical trials, both ketamine (10), an NMDA receptor antagonist, and lamotrigine (11), which inhibits the release of glutamate, have been reported to have beneficial effects on CP. However, in the only study evaluating the use of dextromethorphan to treat CP this drug was not found to be of benefit (3). Possible reasons for this include binding to a different subtype of NMDA receptor, the relatively small doses of dextromethorphan used (27 mg tid versus 90 mg tid in our patient), the psychomimetic effects of ketamine, and the local and general anesthetic properties of the drug. In view of previous reports indicating dextromethorphan to be effective in treating other types of neuropathic pain, (12) we feel this issue requires reexamination.

Whereas our patient’s symptoms were strongly indicative of CP, several factors concerned us. One was the rapid worsening of pain over a six-week period from a pathologic process that probably took years to evolve. This may have been because the hemangiomas needed to reach a critical size to impinge on thalamocortical pain pathways. Indeed, several authors have shown there is no difference in the tendency to cause CP between rapidly developing processes, such as infarcts and hemorrhages, and those that develop more slowly, like arteriovenous malformations (13).

A second point that concerned us was how congenital or slowly developing venous hemangiomas could lead to the development of CP. The reason venous malformations rarely lead to neurologic sequelae is because they do not generally result in vascular compromise. In patients with a rapidly expanding cerebral blood vessel, a new neurologic deficit resulting from edema, microhemorrhage, or vasospasm in the surrounding brain is a possibility. However, these entities would be more likely to cause temporary symptoms and would probably be detected on MRI. A more plausible hypothesis is that the sheer size and number of lesions in our patient interfered with thalamocortical pain pathways because of a mass effect.

Last, we required an explanation for the patient’s sudden development of tension-type headaches. Whereas almost any cerebral vascular abnormality can manifest as head pain secondary to local ischemia or a mass effect, one study suggested that central sensitization of supraspinal neurons may be responsible for tension-type headaches (14). A simpler theory is that they were transformed migraines precipitated by pain-related stress.

An alternative explanation for our patient’s presentation is that the dilated cerebral veins resulted from an acute venous thrombosis that led to regional areas of ischemia. This would explain the late and relatively abrupt onset of our patient’s symptoms. This has been described, although never in the context of causing CP. An angiogram, which we were unable to obtain, might have provided a definitive diagnosis.

Even when diagnosed early, the prognosis for complete eradication of CP is poor, as can be evidenced by the response of our patient. Nevertheless, in the absence of a surgically treatable lesion, pharmacologic therapy with anticonvulsants, sodium channel blockers, tricyclic antidepressants, NMDA antagonists, and opioids may result in significant improvement. Drug classes that have shown promise in preclinical trials include calcitonin-gene related peptide antagonists and 5-hydroxytryptamine and adenosine agonists (15–17). For refractory cases, motor cortex stimulation can bring relief to some patients (18).

In conclusion, this case study describes a woman with symptoms strongly suggestive of CP who was noted to have multiple, giant cerebral venous malformations contralateral to her pain complaints. It is the first reported association between venous malformations and CP. In view of our patient’s response to dextromethorphan, this case underscores the need for further evaluation of NMDA antagonists in this disorder.

The authors gratefully acknowledge David Bowsher, MD, ScD, PhD, Pain Research Institute, University Hospital Aintree, Liverpool, United Kingdom, for his helpful comments.

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© 2002 International Anesthesia Research Society