Intrathecal morphine for Restless Legs Syndrome

Intrathecal morphine for Restless Legs Syndrome

For those who suffer from a medically refractory Restless Legs Syndrome (RLS), intrathecal morphine treatment has been shown to be effective. The aim of a retrospective study of Steensland et al. was to investigate efficacy, complications and side effects in patients treated over several years with an implantable pump. A comparison was done to a group of patients treated with a similar pump system due to spasticity.

The charts of ten patients with severe or very severe RLS have been reviewed. These patients have received an intrathecal drug delivery system during 2000 -2016. To compare the rate of complications, a control group of 20 patients treated with intrathecal baclofen due to spasticity was included in the study. Their time of treatment corresponded to the RLS patients’.

The severity of symptoms related to RLS decreased significantly after treatment. Doses required ranged from 68 to 140 µg/day. Two cases of side effects were detected; one case with nausea and dizziness and one case with headache and fatigue. The rate of mechanical-, infectious- and other complications were similar between the two groups.

In light of the decrease in symptom severity and the low rate of side effects, intrathecal morphine can be considered an adequate treatment for those suffering from medically refractory RLS. The occurrence of complications did not differ between subjects with RLS and spasticity 1).

Case reports

Three patients with medically refractory RLS received an implanted pump for delivery of intrathecal morphine. Severity of RLS and self-assessed health were rated using the International Restless Legs Syndrome Study Group (IRLSSG) rating scale and the Short Form health survey (SF-36). Assessments were made preoperatively and after 6 months of follow-up.

Preoperatively two patients had very severe RLS, scoring 35 and 36 on the IRLSSG rating scale, and one patient had severe RLS (score, 26). All three patients were free of symptoms of RLS post-operatively and also at the 6-month follow-up. The daily doses of intrathecal morphine ranged from 73 to 199 µg. Results from the SF-36 health survey showed that all three patients had a better physical health compared to before surgery.

Intrathecal morphine may be efficient in the treatment for medically refractory RLS. All three patients became completely free of symptoms, and there was also improvement in self-perceived overall health 2)


In 2012 case reports of 4 patients documented excellent results with short-term use of intrathecal opioids also in RLS 3).


In 2008 Ross et al. reported the successful use of low-dose intrathecal morphine in a severe case of restless legs syndrome refractory to medication.

The surgery was complicated by extreme restlessness in the recovery room resulting in withdrawal or breakage of the catheter on multiple occasions. Relief of symptoms was lost with each catheter malfunction. They describes the possible origin of this complication and a solution to the problem resulting in the successful control of symptoms for 7 months since the last surgery. 4).

They are, however, wrong in their statement that this is the third published case of this particular treatment. In an article in the Swedish medical journal Lakartidningen 5), Lindvall et al. previously accounted for 7 patients with refractory restless legs syndrome who were successfully treated with intrathecal morphine. An abstract in English is available through the official web site of this journal, and the article is indexed by PubMed. The 7 patients were treated at 3 hospitals in the northern region of Sweden, which is covered by the neurosurgical department of Umeå University Hospital 6).


In 2002 two patients with incapacitating symptoms from restless legs syndrome, not adequately responding to conventional treatment with dopaminergic drugs, were implanted with a pump device (Isomed) for intrathecal delivery of morphine and bupivacaine. The treatment resulted in total resolution of all symptoms with few side effects 7).

References

1)

Steensland I, Koskinen LD, Lindvall P. Treatment of Restless legs with a pump; efficacy and complications. Acta Neurol Scand. 2019 Dec 28. doi: 10.1111/ane.13213. [Epub ahead of print] PubMed PMID: 31883387.
2)

Lindvall P, Hariz GM, Blomstedt P. Overall self-perceived health in Restless legs treated with intrathecal morphine. Acta Neurol Scand. 2013 Apr;127(4):268-73. doi: 10.1111/j.1600-0404.2012.01707.x. Epub 2012 Aug 9. PubMed PMID: 22881705.
3)

Hornyak M, Kaube H. Long-Term treatment of a patient with severe restless legs syndrome using intrathecal morphine. Neurology. 2012 Dec 11;79(24):2361-2. doi: 10.1212/WNL.0b013e318278b5e7. Epub 2012 Nov 28. PubMed PMID: 23197746.
4)

Ross DA, Narus MS, Nutt JG. Control of medically refractory restless legs syndrome with intrathecal morphine: case report. Neurosurgery. 2008 Jan;62(1):E263; discussion E263. doi: 10.1227/01.NEU.0000311089.04014.91. PubMed PMID: 18300885.
5)

Lindvall PK, Ruuth K, Jakobsson B, Nilsson SK. [Intrathecal morphine infusion a possible treatment in restless legs]. Lakartidningen. 2007 Aug 8-21;104(32-33):2250-2. Swedish. PubMed PMID: 17822205.
6)

Lindvall P, Ruuth K, Jakobsson B, Nilsson S. Intrathecal morphine as a treatment for refractory restless legs syndrome. Neurosurgery. 2008 Dec;63(6):E1209; author reply E1209. doi: 10.1227/01.NEU.0000325674.02282.CC. PubMed PMID: 19057291.
7)

Jakobsson B, Ruuth K. Successful treatment of restless legs syndrome with an implanted pump for intrathecal drug delivery. Acta Anaesthesiol Scand. 2002 Jan;46(1):114-7. PubMed PMID: 11903084.

Klippel Feil syndrome

Klippel Feil syndrome

Klippel Feil syndrome is a rare disease, initially reported in 1912 by Maurice Klippel and André Feil from France, characterized by the congenital fusion of any 2 of the 7 cervical vertebrae.

Congenital fusion of two or more cervical vertebrae. Ranges from the fusion of only the bodies (congenital block vertebrae) to fusion of the entire vertebrae (including posterior elements). Results from failure of normal segmentation of cervical somites between 3 and 8 weeks’ gestation. Involved vertebral bodies are often flattened, and associated disc spaces are absent or hypoplastic. Hemivertebrae may also occur. Neural foramina are smaller than normal and oval. Cervical stenosis is rare. The complete absence of the posterior elements with an enlarged foramen magnum and fixed hyperextension posture is called iniencephaly and is rare. The incidence of Klippel-Feil is unknown due to its rarity and the fact that it is frequently asymptomatic.

May occur in conjunction with other congenital cervical spine anomalies such as basilar impression and atlantooccipital fusion.

Classification

Samartzis classification

Type I Having a single congenitally fused cervical segment.

Type II Multiple noncontiguous, congenitally fused segments.

Type III Multiple contiguous, congenitally fused cervical segments 1)


Type I: mass fusion of C-spine to upper T-spine

Type II: fusion of only 1 or 2 interspaces

Clinical features

Classic clinical triad (all 3 are present in < 50%):

1. low posterior hairline

2. shortened neck (brevicollis)

3. limitation of neck motion (may not be evident if < 3 vertebrae are fused, if fusion is limited only to the lower cervical levels, or if hypermobility of nonfused segments compensates). Limitation of movement is more common in rotation than flexion-extension or lateral bending

Other clinical associations include scoliosis in 60%, facial asymmetry, torticollis, webbing of the neck (called pterygium colli when severe), Sprengel’s deformity in 25–35% (raised scapula due to failure of the scapula to properly descend from its region of formation high in the neck to its normal position about the same time as the Klippel-Feil lesion occurs), synkinesis (mirror motions, primarily of hands but occasionally arms also), and less commonly facial nerve palsy, ptosis, cleft or high arched palate. Systemic congenital abnormalities may also occur, including genitourinary (the most frequent being a unilateral absence of a kidney), cardiopulmonary, CNS, and deafness in ≈ 30% (due to defective development of the osseous inner ear).

No neurologic symptoms have ever been directly attributed to the fused vertebrae, however, symptoms may occur from nonfused segments (less common in short-segment fusions) which may be hypermobile, possibly leading to instability or degenerative arthritic changes.


The syndrome occurs in a heterogeneous group of patients unified only by the presence of a congenital defect in the formation or segmentation of the cervical spine. Klippel–Feil syndrome can be identified by shortness of the neck. Those with the syndrome have a very low hairline and the ability of the neck to move is limited.

Treatment

Usually directed at detecting and managing the associated systemic anomalies. Patients should have a cardiac evaluation (EKG), CXR, and renal ultrasound. Serial examinations with lateral flexion-extension C-spine X-rays to monitor for instability. Occasionally, a judicious fusion of an unstable non-fused segment may be needed at the risk of further loss of mobility.


In patients with KFS with basilar invagination (BI), compression of the brainstem and upper cervical cord results in neurological deficits, and decompression and occipitocervical reconstruction are required. The highly varied anatomy of KFS makes a posterior occipitocervical fixation strategy challenging. For these patients, the transoral atlantoaxial reduction plate (TARP) operation is an optimal option to perform a direct anterior fixation to achieve stabilization 2).


Contraindications for participation in contact sports except associated with full ROM without occipitocervical anomalies, instability, disc disease absolute or degenerative changes.

Outcome

In the series Patel et al. the patients who pursued surgical treatment reported significantly more comorbidities (p = 0.02) and neurological symptoms (p = 0.01) than nonsurgically treated participants and were significantly older when pain worsened (p = 0.03), but there was no difference in levels of muscle, joint, or nerve pain (p = 0.32); headache/migraine pain (p = 0.35); total number of cervical fusions (p = 0.77); location of fusions; or age at pain onset (p = 0.16).

More than 90% of participants experienced pain. Participants with an increased number of overall cervical fusions or multilevel, contiguous fusions reported greater levels of muscle, joint, and nerve pain. Participants who pursued surgery had more comorbidities and neurological symptoms, such as balance and gait disturbances, but did not report more significant pain than nonsurgically treated participants 3).

Case series

Seventy-five patients (60 female, 14 male, and 1 unknown) were identified and classified as having the following types of Samartzis fusion: type I, n = 21 (28%); type II, n = 15 (20%); type III, n = 39 (52%). Seventy participants (93.3%) experienced pain associated with their KFS. The median age of patients at pain onset was 16.0 years (IQR 6.75-24.0 years), and the median age when pain worsened was 28.0 years (IQR 15.25-41.5 years). Muscle, joint, and nerve pain was primarily located in the shoulders/upper back (76%), neck (72%), and back of head (50.7%) and was characterized as tightness (73%), dull/aching (67%), and tingling/pins and needles (49%). Type III fusions were significantly associated with greater nerve pain (p = 0.02), headache/migraine pain (p = 0.02), and joint pain (p = 0.03) compared to other types of fusion. Patients with cervical fusions in the middle region (C2-6) tended to report greater muscle, joint, and nerve pain (p = 0.06). Participants rated the effectiveness of oral over-the-counter medications as 3 of 5 (IQR 1-3), oral prescribed medications as 3 of 5 (IQR 2-4), injections as 2 of 5 (IQR 1-4), and surgery as 3 of 5 (IQR 1-4), with 0 indicating the least pain relief and 5 the most pain relief. Participants who pursued surgical treatment reported significantly more comorbidities (p = 0.02) and neurological symptoms (p = 0.01) than nonsurgically treated participants and were significantly older when pain worsened (p = 0.03), but there was no difference in levels of muscle, joint, or nerve pain (p = 0.32); headache/migraine pain (p = 0.35); total number of cervical fusions (p = 0.77); location of fusions; or age at pain onset (p = 0.16).

More than 90% of participants experienced pain. Participants with an increased number of overall cervical fusions or multilevel, contiguous fusions reported greater levels of muscle, joint, and nerve pain. Participants who pursued surgery had more comorbidities and neurological symptoms, such as balance and gait disturbances, but did not report more significant pain than nonsurgically treated participants 4).

References

1)

Samartzis DD, Herman J, Lubicky JP, Shen FH. Classification of congenitally fused cervical patterns in Klippel-Feil patients: epidemiology and role in the development of cervical spine-related symptoms. Spine (Phila Pa 1976). 2006 Oct 1;31(21):E798-804. PubMed PMID: 17023841.
2)

Wei G, Wang Z, Ai F, Yin Q, Wu Z, Ma XY, Xu J, Shi C, Xia H. Treatment of Basilar Invagination With Klippel-Feil Syndrome: Atlantoaxial Joint Distraction and Fixation With Transoral Atlantoaxial Reduction Plate. Neurosurgery. 2016 Apr;78(4):492-8. doi: 10.1227/NEU.0000000000001094. PubMed PMID: 26990409.
3) , 4)

Patel K, Evans H, Sommaruga S, Vayssiere P, Qureshi T, Kolb L, Fehlings MG, Cheng JS, Tessitore E, Schaller K, Nouri A. Characteristics and management of pain in patients with Klippel-Feil syndrome: analysis of a global patient-reported registry. J Neurosurg Spine. 2019 Dec 13:1-6. doi: 10.3171/2019.9.SPINE19820. [Epub ahead of print] PubMed PMID: 31835254.

Tethered cord syndrome treatment

Tethered cord syndrome treatment

Tethered cord can cause neurological, orthopaedic and sphincteric problems in children and detethering surgery may prevent or reverse these problems.

In adults, if the only abnormality is a thickened, shortened filum, then a limited lumbosacral laminectomy may suffice, with division of the filum once identified. If a lipoma is found, it may be removed with the filum if it separates easily from neural tissues.

The filum is differentiated from nerve roots by the presence of characteristic squiggly vessel on the surface of filum. Also, under the microscope, the filum has a distinctively whiter appearance than the nerve roots, and ligamentous-like strands can be seen running through it. NB: intra-op electrical stimulation and recording of anal sphincter EMG are more definitive.

Untethering (tethered cord release) is the gold standard treatment for TCS. However, untethering carries risks of spinal cord injury and postoperative retethering 1)

Intraoperative MEP improvement occurs in about 50 % of the patients following successful untethering. This finding probably provides support to the ischemic theory of tethered cord syndrome.

Surgical detethering led to a reduction in the CSF levels of the markers of anaerobic metabolism and neuronal injury. There was also a reduction in the latencies of the SSEP waves, indicating better electrophysiologic functioning of the cord 2)

Shifting the tethered cord and lipoma to the dorsal side by harnessing the lumbar lordosis instead of detethering, is a viable treatment option for tethered cord syndrome 3).


Although some associated syrinxes improved after surgery for tethered cord, radiological improvement was not consistent and did not appear to be associated with change in clinical symptoms. The decision to surgically untether a cord should be focused on the clinical symptoms and not the presence of a syrinx alone 4).


Early untethering of the cord may result in improvement of scoliosis; however, untethering must be done when the scoliosis is mild. When cases of≤10° scoliosis were untethered, 68% had neurologic improvement and the remaining 32% were stabilized, whereas when scoliosis is severe (≥ 50°) ≈ 16% deteriorated.

References

1)

Kokubun S, Ozawa H, Aizawa T, Ly NM, Tanaka Y. Spine-shortening osteotomy for patients with tethered cord syndrome caused by lipomyelomeningocele. J Neurosurg Spine. 2011 Jul;15(1):21-7. doi: 10.3171/2011.2.SPINE10114. Epub 2011 Apr 15. PubMed PMID: 21495816.
2)

Maurya VP, Rajappa M, Wadwekar V, Narayan SK, Barathi D, Madhugiri VS. Tethered cord syndrome – a study of the short term effects of surgical detethering on markers of neuronal injury and electrophysiologic parameters. World Neurosurg. 2016 Jul 12. pii: S1878-8750(16)30524-1. doi: 10.1016/j.wneu.2016.07.005. [Epub ahead of print] PubMed PMID: 27422680.
3)

Murata Y, Kanaya K, Wada H, Wada K, Shiba M, Kato Y. Reduction of caudal traction force using dural sac opening rather than spinal cord detethering for tethered cord syndrome caused by lipomyelomeningocele: a case report. Spine J. 2014 Oct 1;14(10):e1-3. doi: 10.1016/j.spinee.2014.02.031. Epub 2014 Mar 5. PubMed PMID: 24613376.
4)

Bruzek AK, Starr J, Garton HJL, Muraszko KM, Maher CO, Strahle JM. Syringomyelia in children with closed spinal dysraphism: long-term outcomes after surgical intervention. J Neurosurg Pediatr. 2019 Dec 13:1-7. doi: 10.3171/2019.9.PEDS1944. [Epub ahead of print] PubMed PMID: 31835253.
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