Radiation Oncology/CNS/Cluster Headaches

Chronic Cluster Headaches

• Sudden onset of unilateral pain, typically originating around the eyes, temple, cheek, and forehead. Typically along the V1 division of the trigeminal nerve
• Frequently with concurrent ipsilateral autonomic activity, resulting in ptosis, miosis, lacrimation, conjunctival injection, rhinorrhea, and nasal congestion
• Epidemiology
  • Prevalence of cluster headaches is estimated at 0.2%; incidence at 2-10/100,000
    • ~10% develop chronic cluster headaches (remissions <30 days or duration >1 year)
    • ~20& of CCH patients are highly refractory to medical treatment
  • Male 6:1 female predominance
  • Mean age of onset 30 years
  • Seasonal predilection for spring and fall
  • Increased incidence in monozygotic twins; 14x risk in first-degree relative and 2x risk in second-degree relative suggests role for genetic factors
• Pathophysiology is not clear, but clinical presentation and functional imaging suggests central origin, with posterior hypothalamic hyperactivity. However, the pterygopalatine ganglion may also be involved, due to confluence of multiple nerve fibers passing through
• Multiple surgical modalities (e.g. surgical sectioning of various nerves, MVD, deep brain stimulation, etc) have been explored, but all involved potential complications from surgery
• Deep brain stimulation has proven to effective in both reducing pain and increasing efficacy of pain medications
• Gamma Knife treatment targeting trigeminal nerve has not been successful, and has had much higher rate of side effects than same protocol used safely for trigeminal neuralgia. It is not clear whether the trigeminal nerve is more sensitive to RT in cluster headaches or more resistant to RT in trigeminal neuralgia
• A single case report from Stanford suggest targeting the pterygopalatine ganglion at a lower dose might be efficacious

• Stanford; 2007 PMID 17327771 -- "Cyberknife targeting the pterygopalatine ganglion for the treatment of chronic cluster headaches." (Lad SP, Neurosurgery. 2007 Mar;60(3):E580-1; discussioin E581.)
  • Case report. SRS targert to pterygopalatine ganglion; 45.5 Gy to 78% isodose line (Dmax 65 Gy)
  • Outcome: Good pain control

• Minnesota; 2006 (1997-2001) PMID 17277688 -- "Long-term results of radiosurgery for refractory cluster headache." (McClelland S, Neurosurgery. 2006 Dec;59(6):1258-62; discussion 1262-3.)
  • Retrospective. 10 patients with refractory CH. GKS 75 Gy at 100% isodose to most proximal part of trigeminal nerve, with 50% isodose line outside brain stem. Median F/U 3.3 years
  • Outcome: pain relief fair in 1/10 and poor in 9/10 patients.
  • Toxicity: 50% facial numbness
  • Conclusion: no sustained pain relief when targetting TN

• Marseille
  • Prospective trial. 10 patients. GKS target cisternal segment of trigeminal nerve. Dmax 80-85 Gy. Brainstem dose 4-11.1 Gy.
  • 2006 PMID 17277687 -- "Trigeminal nerve radiosurgical treatment in intractable chronic cluster headache: unexpected high toxicity." (Donnet A, Neurosurgery. 2006 Dec;59(6):1252-7; discussion 1257.) Median F/U 3 years
    • Outcome: 2/10 CR, 1/10 good result, 7/10 no improvement.
    • Toxicity: 90% disturbances (3/10 paresthesia, 6 hypoesthesia including 2 deafferentation pain)
    • Conclusion: High rate of toxicity and failure, despite same methodology ast TN. Do not recommend for intractable CCH
  • 2005 PMID 15654036 -- "Gamma knife treatment for refractory cluster headache: prospective open trial." (Donnet A, J Neurol Neurosurg Psychiatry. 2005 Feb;76(2):218-21.) Mean F/U 1 year
    • Outcome: 3/10 patients no pain, 3/10 patients few attacks, 4/10 no improvement
    • Toxicity: 50% injury (3/10 paresthesia, 1/10 hypoaesthesia, 1/10 deafferentation pain)
    • Conclusion: Rate and severity of nerve injury unexpectedly high; procedure less attractive

• Ford Headache Clinic; 1998 (Alabama) PMID 9504996 -- "Gamma knife treatment of refractory cluster headache." (Ford RG, Headache. 1998 Jan;38(1):3-9.)
  • Case report. 6 patients. Dmax 70 Gy to CNV entry zone. Follow up 8-14 months
  • Outcome: 4/6 excellent relief, 1/6 good relief, 1/6 fair relief
  • Toxicity: none
  • Conclusion: GKS affords great promise with negligible risk