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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 2  |  Issue : 3  |  Page : 93-98

Management of spasticity with intrathecal phenol injections: The past and the present


1 Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
2 Department of Rehabilitation Medicine, The Royal Hospital for Neurodisability, Putney, London, UK
3 Department of Rehabilitation Medicine, NMC Provita, Al Ain, Abu Dhabi, United Arab Emirates

Date of Submission15-Jan-2019
Date of Acceptance15-Mar-2019
Date of Web Publication29-Aug-2019

Correspondence Address:
Dr. Fahim Anwar
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge
UK
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jisprm.jisprm_49_19

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  Abstract 


Introduction: Spasticity is increased, involuntary, velocity-dependent muscle tone that causes resistance to movement. Intrathecal injection of phenol is a form of treatment used in a very selective group of patients with spasticity. Aim: This study aims to highlight current evidence in the treatment of spasticity with intrathecal neurolytic phenol injections. Materials and Methods: A computer-based literature search was performed using MEDLINE, EMBASE, CINAHL, and the Cochrane Library using the following key words: intrathecal, phenol, spasticity, and pain. Results: The search identified 83 articles. Of 16 articles met the inclusion criteria of being specifically relating to the use of intrathecal phenol injections in spasticity. There was a lack of randomized controlled studies addressing intrathecal phenol injections in our search. Conclusions: Intrathecal phenol can be valuable for the treatment of spasticity when adapted for each individual, and used as part of an overall program that includes multidisciplinary team assessment and goal planning.

Keywords: Intrathecal, pain, phenol, spasticity


How to cite this article:
Anwar F, Antiga S, Mee H, Al Khayer A. Management of spasticity with intrathecal phenol injections: The past and the present. J Int Soc Phys Rehabil Med 2019;2:93-8

How to cite this URL:
Anwar F, Antiga S, Mee H, Al Khayer A. Management of spasticity with intrathecal phenol injections: The past and the present. J Int Soc Phys Rehabil Med [serial online] 2019 [cited 2019 Sep 15];2:93-8. Available from: http://www.jisprm.org/text.asp?2019/2/3/93/264783




  Introduction Top


Spasticity was first described by Lance[1] as“a motor disorder, which is characterized by velocity-dependent increased in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex, as one component of the upper motor neuron syndrome.”It is a neurological condition, which can cause muscle stiffness, different types of flexor and extensor deformities in both upper and lower extremities, painful spasms, restriction in the movement of joints, loss of function in arms and legs, and difficulty in walking. These problems cause patients to have difficulties in coping with daily activities, sexual function, maintaining their posture, and ensuring their personal hygiene. As a result, patients may suffer from low mood, social isolation, and problems with family and social relationships.

It has been known that permanent loss of joint range occurs within 3–6 weeks in most of the neurological disorders. Early recognition and treatment are therefore crucial in the management of spasticity. If not treated, spasticity could lead to muscle shortening and joint deformities affecting the overall management of the patient. The treatment of spasticity is not always easy, and the focus should be on improving the overall functional status of the patient.[2] The treatment of spasticity involves wide varieties of physical modalities, pharmacological interventions, botulinum toxins, nerve and motor point blocks with phenol,[3],[4] orthopedic (tendon lengthening and release), and neurosurgical procedures (dorsal rhizotomy and intrathecal baclofen pump insertion). The use of botulinum toxin injections to treat focal spasticity has revolutionized the management of the patient with this disabling condition. Chemical neurolysis with phenol has been reported in the literature to be effective for the treatment in patients with spasticity and pain.[5]

For this review, relevant articles that highlight the treatment of both spasticity and pain with intrathecal phenol injections were identified using several databases.


  Materials and Methods Top


A comprehensive computer-based literature search was performed using MEDLINE, EMBASE, CINAHL, PubMed, and the Cochrane Library Databases using the following keywords: intrathecal, phenol, spasticity, and pain before the October 2, 2018. The research strategy included studies investigating the role of intrathecal phenol in the management of spasticity. Medical subject heading (MeSH) search was used for all databases followed by the keyword search if MeSH term was not available. The references of the identified studies were examined for additional references and to extend the search. A manual search of the relevant journals was undertaken. Guidelines for the management of spasticity from national and international organizations were also examined to look for additional related materials.

Inclusion criteria

Studies that included the use of intrathecal phenol in the treatment of spasticity were included in the review.

Exclusion criteria

The exclusion criteria included; non-English language studies, studies involving pediatric populations, review articles, letter to the editors, conference proceedings, animal studies, and histopathological studies.

Study selection

The abstracts and titles of all the studies identified based on the inclusion criteria were shortlisted and screened by the first two authors. Both the authors independently evaluated the studies. The full text of the selected articles was obtained for further assessment to determine whether they met the inclusion/exclusion criteria.

Data extraction

A standard pro forma was developed to extract the data from the selected studies. The data that were collected comprised of publication date, study design, sample size, number of procedures/injections, type of phenol used, indication for the procedure/injection, transient and permanent complications, and the outcome of the procedure/injection. Formal levels of evidence were assigned using a standard format defined by the National Health and Medical Research Council pilot program 2005–2006 for intervention studies.[6]


  Results Top


We found 83 articles specifically related to the use of intrathecal phenol injections either in spasticity or pain. Of these, only 16 articles were related to the use of intrathecal phenol in spasticity (±pain). There were 24 articles on the use of intrathecal phenol in chronic pain without the involvement of spasticity, 18 review articles, 11 articles were in foreign language, 4 articles were letters to the editors, 2 articles were related to animal studies, and 3 articles were either histological or neuropathological studies. We also found 4 articles related to the unusual complications following the use of intrathecal phenol either in spasticity or pain. The articles that were included in this review were 16 related to the use of intrathecal phenol. [Figure 1] shows the flow diagram of the article's exclusion and inclusion criteria.
Figure 1: PRISM flow diagram of the study selection process

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There is a lack of randomized controlled studies addressing intrathecal phenol injections in our search. The articles were mainly case series or case reports. The 16 articles included 301 patients and 481 intrathecal procedures related to the treatment of spasticity [Table 1]. Eleven studies were case series involving >2 patients whereas 3 studies were case reports involving 1 or 2 patients. There was 1 observational cross-sectional study and 1 retrospective case notes review. There were no reported prospective studies found in the literature. The first study was published in 1959.
Table 1: Studies with intrathecal use of phenol for spasticity

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In nine studies, the authors used phenol in glycerol (various concentration from 2% to 20%), 5 studies mentioned the combined use of phenol in glycerol and phenol in myodil (5%–20%). Only one study mentioned the use of phenol in glycerol and metrizamide, and one study did not mention the type of agent that they used. Four studies did not mention the indication for intrathecal phenol injections, 3 studies mentioned“Spasticity due to Upper Motor Neuron Lesion”as the indications,“Spasticity in lower Limbs”was an indication in 3 studies,“Spasticity in Multiple Sclerosis”in 2 studies,“Paraplegia/Paraparesis”in 2 studies, Spastic Quadriplegia in 1 study and only 1 study included the indication as“Reflex Spasms and Spasticity [Table 2].
Table 2: Studies with intrathecal use of phenol for spasticity, indications, and complications

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Eleven studies reported transient complications which included: bladder dysfunctions (5 studies), sensory symptoms (5 studies), headaches (2 studies), weakness (1 study), and bowel dysfunctions (1 study). Permanent complications were recorded in two studies only, and they were permanent bladder dysfunction in both studies and bedsores in one. Of 16 studies identified, 14 reported good results with a reduction in spasticity, spasms, and pain.


  Discussion Top


Phenol was first discovered in 1834 and has been used for the treatment of spasticity since the 1960s.[4] Aqueous solutions of phenol are available in 5%–7% concentration and is usually used for peripheral nerve neurolysis and motor point blocks to treat spasticity. At low concentrations (<2%) phenol can be used as a short-term anesthetic with minimal nerve injury. At higher concentrations, phenol causes nerve destruction by inducing protein precipitation, loss of cellular fatty elements, separation of the myelin sheath from the axon, and axonal degeneration.[23] Data indicate that at concentrations of 5%–7% phenol may cause a minimum of second-degree nerve injury with minimal to no loss of the endoneurial nerve structure.[24]

Phenol is soluble in glycerin, alcohol, fixed and volatile oils, ether and chloroform. Phenol in glycerin has traditionally been used to treat spasticity through intrathecal route. The addition of glycerin makes the solution thicker and minimizes the risk of spread to higher levels once injected through this route. Our search also showed that phenol with myodil was used in four studies.[8],[7],[10],[13] However, the use of phenol with myodil has not gained popularity as myodil in combination with phenol was found to be much less efficacious than that of phenol in glycerin.[9] In the Liversedge and Maher[9] study, the reason for not using the phenol with myodil was reported to be that phenol was released more slowly from the myodil, and the glycerin-phenol mixture was absorbed directly on to the nerve roots whereas the myodil remained in globular emulsive form reducing its effects on the nerve roots.

The first reported use of intrathecal phenol was published in 1959 by two authors Nathan[8] and Kelly and Guatier-Smith[7] Nathan describes the treatment of 25 patients, 18 of whom had disseminated sclerosis, while Kelly and Gautier-Smith treated 32 patients, of whom 20 had disseminated sclerosis. The other patients had a variety of lesions such as extradural abscess, cerebral hemorrhage, amyotrophic lateral sclerosis, or tumor. Results were in general very good in both these case series. Nathan[8] reported that in 16 of 25 patients, the severe spasm was abolished while in 7 others, it was much reduced and became painless. Similarly, bedridden patients were able to sit up in a wheelchair, and some voluntary movements that had been prevented by spasticity became apparent. Both studies did not report any permanent side effects. Kelly and Gautier-Smith[7] mentioned few complications; two patients had a headache after injection, but it cleared within 24 h, and three patients had leg pain after the procedure, but this also cleared in few days. Bladder disturbance occurred occasionally, and some transient numbness of the leg affected many patients in both the studies.[7],[8]

The duration of action of intrathecal phenol in reducing spasticity is variable depending on the diagnosis, severity, and extent of the spasticity. Liversedge and Maher[9] reported immediate cessation of pain and flexor spasms in an elderly patient who developed spastic leg flexion paralysis as a result of a cerebrovascular accident. The effects of the intrathecal phenol in this case were noted even after 3 years. This prolonged duration of action is very useful in treating severely disabled patients who are unable to attend frequent clinical appointments for other modes of treatment such as botulinum toxin injections.

Spasticity in progressive multiple sclerosis is very difficult to treat, as it is widespread. The main aims are to reduce the carer burden, reduce pain and spasms, and improve the quality of life. Jarrett et al.[20] in 2002 published their cross-sectional data from 25 patients with progressive multiple sclerosis, who underwent intrathecal phenol for spasticity. All patients demonstrated reduced lower limb spasticity bilaterally with significant improvement on the targeted as compared with the nontargeted side. Twenty-four patients were easier to position, and 21 had a reduction in their spasm frequency and intensity. Carers found washing and dressing easier in 16 patients and improved safety when using the hoist in 10. The study used multidisciplinary assessment as a part of an overall program which included patient selection, ongoing treatment, education, measurement, and injection. The multidisciplinary assessment was key to effective patient selection. Browne and Catton[17] presented two cases of multiple sclerosis with advanced paraplegia (limbs flexed in adduction and flexion), and painful muscle spasms in the legs. Both cases were treated with intrathecal phenol in glycerin. Excellent results were seen in the first patient, but the injection had to be repeated within 5 months. In the second patient, there was a good result in the right leg with some painless residual spasms in the left leg. The authors concluded that intrathecal phenol was a useful method for relieving muscle spasms and pain in the lower extremities in advanced cases of multiple sclerosis, and physiotherapy was essential in achieving the desired outcomes.[17]

The more recent case series by Pinder et al.[21] treated 40 patients with intrathecal phenol over 10 years. All patients had improvements in their spasticity, 34 of which were rated as substantial or excellent. All patients except one had a short-term improvement in the goals of treatment; 31 having substantial or excellent improvement. The study also demonstrated the long duration of action of intrathecal phenol, where only 7 patients required repeat injections with similar outcomes.[21] Kandikattu et al.[22] in 2008, also demonstrated that the intrathecal phenol was able to reduce spasticity, spasms, and pain in 20 patients with improvement in patients comfort and ease of nursing care.

Theoretically, the intrathecal phenol effect in reducing the spasticity should be permanent. However, various studies have suggested the return of spasticity in patients previously treated with intrathecal phenol. Iwatsubo et al.[19] injected phenol into the subarachnoid space for severe leg spasms in 15 quadriplegics patients at the T12/Ll interspace. The effectiveness for leg spasm was evaluated by the Penn spasticity and Ashworth rigidity scales. Three patients were completely flaccid whereas 3 patients had minimal, 6 patients had moderate, and 3 patients had a complete recurrence of spasms following the injections. The follow-up period in their study was an average of 13 months. The possible explanation is the nerve fiber regeneration following exposure to the intrathecal phenol.[25] Although the spasms returned in the Iwatsubo et al. study, the authors still concluded that the selective intrathecal block with phenol was significantly valuable in improving the activities of daily living in quadriplegic patients.[19]

The incidence of permanent complications following the intrathecal phenol injections has been very low and only two studies reported permanent bladder weakness[11],[12] and bedsores.[11] Transient bladder weakness, on the other hand, is very common after intrathecal phenol injections.[8],[9],[13],[14],[20] Similarly, in Jarrett et al. series 5 patients developed a change in bowel habits and 2 patients developed fecal incontinence.[20] In clinical practice, patients and relatives are warned about these potential side-effects, and the health-care professionals are recommended to make sure that an appropriate bladder and bowel management plan is in place for the patients. Sensory symptoms, such as paraesthesia,[12] hyperesthesia,[14] and sensory loss[16] were reported as transient side-effects. Although transient, these sensory side-effects could be very disabling for the patients. Greitz and Lindblom[15] used a different technique to inject intrathecal phenol in 10 patients (23 total blocks) to minimize the side-effects. They placed the patients with the spastic side down, injected the local anesthetic followed by a small dose of absorbable and water-soluble contrast medium. Patients were asked to adjust their position unit the contrast medium filled the desired nerve roots followed by the injection of 10% phenol in glycerin. There was a lasting total effect in 10 blocks and lasting partial effect in 6 blocks without any transient or permanent complications [Table 2].

Intrathecal baclofen pumps have been used to treat symptoms of spasticity since the late eighties.[20] As the baclofen is directly delivered to the spinal cord, therefore a very small dose of baclofen can have a significant reduction in spasticity avoiding the side effects of oral baclofen. It is very useful when particularly high doses of baclofen are needed to treat severe spasticity. Compared to the intrathecal phenol, baclofen pump is irreversible as the dose can be adjusted and the pump can be stopped or removed. However, pump insertion is a surgical procedure with its own risk of complications such as infections, catheter blockage, and pump malfunction. If pumps are not filled in time and run out of baclofen, patients can have severe baclofen withdrawal symptoms. Baclofen pump also needs regular refilling, adding to the cost of the pump and procedure. Intrathecal phenol is more appropriate for patients who are not able to attend the regular pump refills due to their advance disability, do not want to take the responsibility of pump refills,[20] where the pump has malfunctioned, and further pump insertion is not possible due to comorbidity, if the patient does not respond to initial intrathecal baclofen trial dose,[26] loose effects on intrathecal baclofen over time[27],[28],[29] or develop tolerance.[29] Some of the advantages of intrathecal phenol over baclofen pump are minimal precautions after the procedure, less individual responsibility, low cost, no requirement of special equipment, and avoiding the regular clinical visits for refills. The reasons of intrathecal phenol not considered as a management option for severe spasticity is its complications (bladder and bowel incontinence, limb weakness, and paraesthesia). Similarly, the widespread use of botulinum toxin injections as the treatment of choice has contributed to the loss of this therapeutic technique, especially in ambulatory patients.[21]


  Conclusions Top


The evidences in the medically established academia for spasticity management using intrathecal phenol injections are limited. Most of these evidences come from case series. The technique appears to be useful as part of an overall management program. With careful patient selection, the procedure is able to provide good results with minimal side effects and complications with a resultant decrease in spasticity and improvement in patient's quality of life.

In today's practice, the technique could be reserved for patients with lower limbs widespread spasticity who are nonambulatory and in whom a baclofen pump insertion is not possible. However, the procedure is better avoided in patients with intact bladder and bowel functions as the phenol within the intrathecal space can damage the nerve supply to the bladder and bowels resulting in permanent bladder and bowel incontinence.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Lance JW. Symposium synopsis. In: Feldmann RG, Young RR, Koella WP, editors. Spasticity: Disordered Motor Control. Miami, FL: Year Book Medical Publishers; 1980.  Back to cited text no. 1
    
2.
Stevenson VL. Rehabilitation in practice: Spasticity management. Clin Rehabil 2010;24:293-304.  Back to cited text no. 2
    
3.
Anwar F, Ramanathan S. Combined botulinum toxin injections and phenol nerve/motor point blocks to manage multifocal spasticity in adults. BJMP 2017;10:a1002.  Back to cited text no. 3
    
4.
Anwar F, Ramanathan S, Khayer A. Complications of peripheral phenol nerve and motor point blocks in the management of spasticity. Int J Ther Rehabil Res 2017;6:1-5.  Back to cited text no. 4
    
5.
Anwar F, Mee H, Ramanathan S. Phenol nerve block for ankle plantar flexor and invertor spasticity in upper motor neuron lesions: A case series. J Int Soc Phys Rehabil Med 2018;1:55-60.  Back to cited text no. 5
  [Full text]  
6.
National Health and Medical Research Council. NHMRC Additional Levels of Evidence and Grades for Recommendations for Developers of Guidelines. National Health and Medical Research Council; December, 2009. Available from: https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf. [Last accessed on 2019 Jul 16].  Back to cited text no. 6
    
7.
Kelly RE, Gautier-Smith PC. Intrathecal phenol in the treatment of reflex spasms and Spasti city. Lancet 1959;2:1102-5.  Back to cited text no. 7
    
8.
Nathan PW. Intrathecal phenol to relieve spasticity in paraplegia. Lancet 1959;2:1099-102.  Back to cited text no. 8
    
9.
Liversedge LA, Maher RM. Use of phenol in relief of spasticity. Br Med J 1960;2:31-3.  Back to cited text no. 9
    
10.
Koppang K. Intrathecal phenol in the treatment of spastic conditions. Acta Neurol Scand Suppl 1962;38:63-8.  Back to cited text no. 10
    
11.
Maher RM. The medical treatment of spasticity. Proc R Soc Med 1964;57:720-3.  Back to cited text no. 11
    
12.
Pedersen E, Juul-Jensen P. treatment of spasticity by subarachnoid phenolglycerin. Neurology 1965;15:256-62.  Back to cited text no. 12
    
13.
Nathan PW. Chemical rhizotomy for relief of spasticity in ambulant patients. Br Med J 1965;1:1096-100.  Back to cited text no. 13
    
14.
Stefanko S, Zebrowski S. Histological changes in the nerve roots and spinal cord after intrathecal administration of phenol for relief of spasticity. Pol Med J 1968;7:1204-8.  Back to cited text no. 14
    
15.
Greitz T, Hannerz J, Lindblom U. Treatment of spasticity with intrathecal block with phenol under myelographic controls. Acta Neurol Scand Suppl 1972;51:437-8.  Back to cited text no. 15
    
16.
Lindblom U. Medical treatment and intrathecal nerve block. Scand J Rehabil Med 1973;5:152-5.  Back to cited text no. 16
    
17.
Browne RA, Catton DV. The use of intrathecal phenol for muscle spasms in multiple sclerosis. A description of two cases. Can Anaesth Soc J 1975;22:208-18.  Back to cited text no. 17
    
18.
Scott BA, Weinstein Z, Chiteman R, Pulliam MW. Intrathecal phenol and glycerin in metrizamide for treatment of intractable spasms in paraplegia. Case report. J Neurosurg 1985;63:125-7.  Back to cited text no. 18
    
19.
Iwatsubo E, Okada E, Takehara T, Tamada K, Akatsu T. Selective intrathecal phenol block to improve activities of daily living in patients with spastic quadriplegia. A preliminary report. Paraplegia 1994;32:489-92.  Back to cited text no. 19
    
20.
Jarrett L, Nandi P, Thompson AJ. Managing severe lower limb spasticity in multiple sclerosis: Does intrathecal phenol have a role? J Neurol Neurosurg Psychiatry 2002;73:705-9.  Back to cited text no. 20
    
21.
Pinder C, Bhakta B, Kodavali K. Intrathecal phenol: An old treatment revisited. Disabil Rehabil 2008;30:381-6.  Back to cited text no. 21
    
22.
Kandikattu S, Ahmed N, Khatoon A, Shepherd J. The lost technique: Intrathecal phenol for the management of lower limb spasticity and pain. Reg Anaesth Pain Med 2008;33:e45.  Back to cited text no. 22
    
23.
Cohen SP. Essential of Pain Medicine. 3rd ed. Philadelphia: Elsevier/Saunders; 2011. p. 532-3.  Back to cited text no. 23
    
24.
Hsu M. Significance of clinical treatments on peripheral nerve and its effect on nerve regeneration. J Neurol Disord 2014;2:168.  Back to cited text no. 24
    
25.
Hansebout RR, Cosgrove JB. Effects of intrathecal phenol in man. A histological study. Neurology 1966;16:277-82.  Back to cited text no. 25
    
26.
Jarrett L, Leary SM. Porter B, Richardson D, Rosso T, Powell M, et al. Managing spasticity in people with multiple sclerosis. A goal-oriented approach to intrathecal baclofen therapy. Int J of MS Care 2001;3:10-25.  Back to cited text no. 26
    
27.
Coffey JR, Cahill D, Steers W, Park TS, Ordia J, Meythaler J, et al. Intrathecal baclofen for intractable spasticity of spinal origin: Results of a long-term multicenter study. J Neurosurg 1993;78:226-32.  Back to cited text no. 27
    
28.
Becker WJ, Harris CJ, Long ML, Ablett DP, Klein GM, DeForge DA, et al. Long-term intrathecal baclofen therapy in patients with intractable spasticity. Can J Neurol Sci 1995;22:208-17.  Back to cited text no. 28
    
29.
Akman MN, Loubser PG, Donovan WH, O'Neill ME, Rossi CD. Intrathecal baclofen: Does tolerance occur? Paraplegia 1993;31:516-20.  Back to cited text no. 29
    


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