Neurofibromatosis 1 associated pain syndromes

Thomas J Geller, MD NF clinic director, CGCH Assoc Prof Neurology, SLU

Frequency of Pain as a complaint in Neurofibromatosis patients

Though numerous neurologic
complications of NF-1 appear (optic gliomas, subcutaneous neurofibromas, macrocephaly, plexiform neurofibromas, seizures, LDs), the most common symptoms causing disability for adult patients are pain symptoms. (11.3 % in Zellers 1 year study of 158 adults)

Headache studies in NF-1

North reports an incidence of 9% of severe

headache. Zeller found adult incidence of disabling headache to be 18%, but did not break out the patients with common migraine. Recurring headache in DiMaurios study occurred in 46% of NF patients; 14% met criteria for migraine, 18% tension headache. Other studies show that migraine incidence in the general population is about 18%, regardless of severity.

Age and Pain in NF-1

Quality of life with painful complications of NF-1

French dermatology study of mixed adult/ ped
NF-1 demonstrated that for all aspects of the general questionnaire, including bodily pain, pts with NF-1 reported lower QOL scores than the general population. Increased severity of the disease was assoc with increased negative effect on bodily pain.

Pediatric NF Pain study

Oostenbrink studied 34 NF Dutch children
from 1 to 6 yrs of age using the infant/toddler QOL index. Added 7 questions on pain and limitations of activity A significant difference in QOL was identified from kids with bodily pain vs those without bodily pain.

Non-headache pain: (bodily pain)

In the 18 adults with chronic pain,
symptoms began in childhood in 7. Pain was felt to be clearly organic in 83%. In 17% the cause was unknown.

Causes of peripheral pain

Peripheral nerve or root- 39% Surgical pain- 22% Malignant peripheral nerve sheath tumor17% plexiform neurofibroma- 11% Subcutaneous neurofibroma-11%

Outcome of peripheral pain in NF-1

77% were able to achieve at least partial

remission of pain. Pain was intermittent in of patients. Chronic pain was complicated by breakthru with movement or contact of the affected nerve region in most patients. Optimal pain management was considered to be analgesics, antidepressants and/or anticonvulsants. Some required neurostimulation or spinal procedures.

Theoretical mechanisms of pain supersensitivity in NF-1

Changes in the excitability of dorsal root
entering the spinal cord Study of sensory cultured neurons reveals enhanced excitability of neurons, and increased release of pain neurotransmitters CGRP and substance P. Anxiety in the subject over the risk of pain being associated with a malignancy

Neuropathic

May be caused by several processes

Direct tumor infiltration

Nerve damage / demyelination

Nerve compression Radiation Chemotherapy (taxols & vincristine) Viral Metabolic

Spontaneous burning Intermittent Radiating Shooting Light touch (allodynia) Sharp Stabbing Pins & needles

Neuropathic

Neuropathic pain mechanisms

Cornerstones of treatment of neuropathic pain

Because neuropathic pain has both
peripheral and central mechanisms of development and enhancement, treatment is probably best when multiple methods of attack are applied. Treatment should be applied early to avoid wind-up mechanisms of enhanced pain

Agents for neuropathic pain

Analgesics including opioids when needed Ketotifen for neurofibromas (esp with itching) Calcium channel blocking anticonvulsants,

(Neurontin and Lyrica) Norepinephrine and serotonin blockers, (tricyclics and Cymbalta) Possibly sodium channel blockers PHYSIOTHERAPY Relaxation therapies Surgical management