RHEUMATOID ARTHRITIS AND ANAESTHESIA - PART 2 ANAESTHESIA TUTORIAL OF THE WEEK 267 : WFSA - Resources (2022)

QUESTIONS

  1. A patient with long standing rheumatoid arthritis (RA) presents with hoarseness of voice. What are the anaesthetic implications of this? Choose the single best answer.
    1. This history is not significant
    2. Hoarseness might worsen after endotracheal intubation-the patient should be warned about this
    3. The patient may be difficult to intubate as the vocal cords may be swollen
    4. The patient probably has cricoarytenoid involvement, which combined with airway oedema post intubation can cause complete airway obstruction in the post operative period.
  2. Regarding anaesthesia for patients with RA (true/false):
    1. Spinal and epidural anaesthesia should be used where possible
    2. Regional nerve blocks are contraindicated
    3. Awake fibreoptic intubation (AFOI) may be needed in cases of severe atlanto-axial subluxation
    4. An LMA can be used for airway management to limit neck manipulation
    5. Cervical spine involement in RA is always accompanied by symptoms
  3. Regarding atlanto axial involvement in RA (true/false):
    1. The most common type of atlanto-axial subluxation (AAS) is posterior AAS
    2. Subluxation exists when the distance between the atlas and the odontoid peg exceeds 4 mm in patients older than 44 and 3 mm in younger patients
    3. Flexion of the neck is more harmful than extension
    4. AAS can be diagnosed only by a CT scan
    5. Severe AAS may necessitate an awake tracheostomy for airway management

INTRODUCTION

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that affects 1-2% of the population. The multisystem nature of the disease, issues with airway management and polypharmacy makes the anaesthetic management of these patients challenging. Anaesthetists may come across patients with RA during orthopaedic surgery relating to their disease, joint injections, incidental surgery, pregnancy and delivery and ICU management.

The aetiopathogenesis, clinical features, diagnosis and treatment of RA are discussed in “Rheumatoid Arthritis and Anaesthesia – part 1” (ATOTW 266). This article focuses on the anaesthetic considerations in patients with RA.

PRE-OPERATIVE ASSESSMENT AND PREPARATION

  • A thorough history of the RA including duration of the disease, severity, drug treatments and systemic complications should be taken.
  • Rheumatoid patients are often in pain and suffer with deformities that restrict simple movements; care should be taken during examination.
  • The range of movement of all joints should be noted so as to optimise patient position and minimise injury during anaesthetic procedures (venous access, nerve blocks) and positioning for surgery. Involvement of the joints of the wrists and fingers may limit function enough topreclude the use of a standard patient-controlled analgesia (PCA).
  • These patients have very fragile skin that is easily damaged. Fragile veins makes peripheral venous access unreliable and central venous access is often difficult due to neck deformity.
  • Preoperative neurological deficit, if any, should be documented.
  • Patients taking more than 10 mg prednisolone per day should be given appropriate peri- operative steroid cover. Patients should continue their regular prednisolone and receive hydrocortisone intra-operatively to cover the stress response to surgery. Depending on the type of procedure, hydrocortisone may need to be continued into the postoperative period as shown in Appendix 1.
  • Patients are likely to have anaemia (normocytic normochromic anaemia due to chronic disease or microcytic anaemia due to gastric bleeding and drug toxicity of bone marrow) and there may be increased requirement for red-cell transfusion.
  • Patients may have cachexia, which is indicative of poorly controlled disease and an increased long-term cardiovascular risk. Cachexia and poor muscle bulk may also indicate myopathy which may impair respiratory muscle function, and such patients may need to be considered for postoperative mechanical ventilation.
  • Methotrexate can be continued in the peri-operative period without impaired wound healing or a substantially raised risk of peri-operative infection1 Furthermore, good disease control in the peri-operative period is beneficial. There is lack of data regarding the use of other immunosuppressants. Peri-operative discontinuation of biological therapy for elective surgery remains controversial. Recent studies have suggested that their use does not cause specific adverse effects and may improve recovery from postoperative anaemia.

Airway assessment

  • A detailed airway assessment including mouth opening, TMJ function, neck flexion and extension is essential.
  • Temporomandibular joint involvement should be assessed pre-operatively using the Mallampati score, mouth opening and mandibular protrusion.
  • Any history of cervical surgery should be elicited, as cervical fixation devices may cause impaired neck extension.
  • There are no published evidence-based guidelines or general consensus on the need to obtain cervical spine X-rays before surgery in asymptomatic patients. However it may be prudent to obtain neck X-rays in long term patients with severe disease.
  • If atlanto-axial subluxation (AAS) is suspected, plain X-ray films in flexion and extension of the neck are often diagnostic. Subluxation exists when the distance between the atlas and the odontoid peg exceeds 4 mm in patients older than 44 years and 3 mm in younger patients. A flexion/extension CT or MRI should be considered if symptoms are associated with severe pain, neurological signs are present or if there is significant abnormality noted on plain X-ray.
  • Fibreoptic nasopharyngoscopy is indicated for patients with hoarseness because of the likelihood of cricoarytenoid involvement

Management of the airway

The issues in airway management are the increased prevalence of a difficult airway (RA patients needing cervical spine surgery have a high prevalence of grade 3 or 4 laryngoscopy) and the presence of AAS, which may result in spinal cord injury during airway management. The extent of neck flexion and extension should be assessed and documented. Peri-operatively, care should be taken to avoid any movement beyond this range.

The risks are dependent on the type of AAS. The most common is anterior AAS (80%), which is worsened by C1/C2 flexion. Direct laryngoscopy is usually well tolerated. Subluxation is worsened by the head moving anteriorly whilst the upper cervical spine remains static, e.g. putting a pillow behind the head. A useful technique is to keep the upper cervical spine supported whilst the head is not moved anteriorly, e.g. using a doughnut head ring with a large enough hole to accommodate the occiput. This supports the cervical spine without anterior movement of the head, and is the best choice for rheumatoid patients.

Posterior and vertical AAS both pose the risk of spinal cord compression during C1/C2 extension, the movement of which occurs during direct laryngoscopy, which should therefore be avoided. They are much less common than anterior AAS, and are mostly symptomatic.

RHEUMATOID ARTHRITIS AND ANAESTHESIA - PART 2 ANAESTHESIA TUTORIAL OF THE WEEK 267 : WFSA - Resources (1)

Figure 1. Cervical spine X-rays in a patient with severe rheumatoid arthritis on long term steroids showing anterior atlanto-axial subluxation (with permission from Oxford University Press). A- extension. B- flexion: Demonstrates severe anterior atlanto-axial subluxation. Note the position of dens axis (arrow). There is a 13 mm dislocation between the dens and the main body of the axis. C3 shows degenerative changes.

Cricoarytenoid arthritis is variable in frequency and often unrecognised. Patients have both joint and soft tissue swelling causing stenosis. Symptoms may include hoarseness, stridor, a sense of pharyngeal fullness when speaking and swallowing or dyspnoea. If cricoarytenoid involvement is suspected, avoid endotracheal inubation in favour of supraglottic airway devices. If intubation is essential, use the smallest internal diameter tracheal tube possible. Problems occur post extubation, when the oedema combined with an already narrow airway can cause complete obstruction. Consider the use of an airway exchange catheter at extubation, and observe patient in a high dependency area for some time post extubation. In severe cases, a pre-operative tracheostomy may be required.

Pre operative investigations

  • Routine full blood count, renal function and electrolytes.
  • Liver function tests in patients on long term disease modifying anti-rheumatic drugs (DMARDs).
  • Low threshold for ordering respiratory investigations (chest radiographs, arterial blood gases and lung function tests) due to the possibility of pulmonary involvement or respiratory myopathy.
  • An ECG should be performed to check for left ventricular hypertrophy and conduction disturbances. An echocardiogram should be performed to look for evidence of diastolic dysfunction, left ventricular hypertrophy and valvular abnormalities. Left ventricular ejection fraction may be normal and falsely reassuring in the presence of diastolic dysfunction.

INTRA-OPERATIVE MANAGEMENT

There is no one recommended anaesthetic technique; choice of technique will depend on the patient’s general condition, type of surgery, patient preference and skill of the anaesthetist. Regional anaesthesia, general anaesthesia or a combination of the two may be employed.

Regional anaesthesia, if possible, should always be considered, as it avoids airway manipulation, provides good postoperative pain relief and reduces polypharmacy. However, regional and neuraxial blocks may be technically difficult due to spinal arthritis and loss of anatomical landmarks from contractures or deformities. A higher than normal level should be anticipated during a subarachnoid block1.

If a general anaesthetic is indicated, there are several options for managing the airway depending on the patient and the type and duration of surgery.

  • Laryngeal mask airways (LMAs) and other supraglottic airway devices have the advantages of requiring minimal neck manipulation for insertion and causing lesser trauma and subsequent laryngeal oedema compared with a tracheal tube. They should be used where possible. Theymay be difficult to insert in patients with fixed flexion deformities of the neck.
  • If tracheal intubation is indicated, neck manipulation should be minimised, ideally with manual in-line stabilisation, even in the absence of overt cervical spine instability. There are no case reports to date of spinal cord injury secondary to direct laryngoscopy, nor is there any evidence of outcome difference with a particular technique. However, all due care must be taken during airway management. The intubating LMA could be used to aid intubation with minimal neck manipulation, although it is not a popular technique due to high risk of failure and associated trauma to the airway.
  • Fibreoptic intubation is considered the appropriate and safer option in rheumatoid patients with an anticipated difficult airway or known cervical spine instability. It generally carries less risk of major difficulties than tracheal intubation using direct laryngoscopy in this subgroup of patients. Awake fibreoptic intubation should be considered in patients with known cervical spine subluxation, as it allows for assessment of neurological symptoms indicating spinal compression. This technique is not useful under emergency conditions, or if excessive blood or secretions are in the airway.
  • A surgical tracheostomy under local anaesthesia may be indicated in emergency situations and in patients who have symptoms of upper airway obstruction.

Intra-operatively, patients with RA present problems with positioning due to joint deformities and fragile skin due to steroid therapy. Pressure points should be meticulously padded, the neck adequately supported and skin handled with care. Excessive manipulation of stiff and fixed joints should be avoided.

It is worth noting that the prolonged, relative spinal malposition during general anaesthesia, in a patient with possible spinal stenosis, may cause cord injury. It has been suggested that the patients position themselves on the operating table before being anaesthetised. Attention to the maintenance of spinal cord perfusion may be important and hypotension should be avoided.

The use of immunosuppressive treatments put patients with RA at an increased risk of infections. Strict aseptic technique should be adopted for intravascular access and regional blocks. Appropriate antibiotic prophylaxis should be given before starting surgery.

POSTOPERATIVE MANAGEMENT

Careful observation of the airway and breathing are required in the immediate postoperative period. Previously asymptomatic cricoarytenoid arthritis may cause airway obstruction postoperatively as a result of the additional oedema caused by tracheal intubation. This may occur several hours postoperatively, necessitate reintubation or in some cases a tracheostomy.

Pain should be adequately controlled to permit early mobilisation. Multimodal analgesia is recommended. Some patients may have chronic pain issues and their pain may be difficult to manage. Opioid analgesia can be used in carefully monitored doses to avoid respiratory compromise. Patients with joint deformities of the hand may not be able to use a standard PCA, but can be instructed in the use of a mouth controlled device.

Patients with RA tend to have a slower recovery and return to mobilisation, and also are considered to be in a hypercoagulable state, hence appropriate thromboprophylaxis should be prescribed. Standard physiotherapy and breathing exercises should be instituted as early as possible due to the increased infection risk. If signs of a postoperative infection develop, DMARDs should be suspended temporarily and appropriate antimicrobials started.

SUMMARY

Anaesthesia for the patient with severe rheumatoid arthritis is challenging. It requires a good knowledge of the multisystem effects of the disease, the drugs used to treat it, and meticulous attention to detail, to safely anaesthetise these patients.

ANSWERS

Answer 1

D

Hoarse voice in a patient with longstanding RA, should lead to suspicion of cricoarytenoid arthritis, which is variable in frequency and often unrecognised. Other symptoms include stridor, a sense of pharyngeal fullness when speaking and swallowing or dyspnoea. Pre operative nasoendoscopy may aid in diagnosis. If cricoarytenoid involvement is suspected, avoid endotracheal int inubation in favour of supraglottic airway devices. If intubation is essential, use the smallest internal diameter tracheal tube possible. Problems occur post extubation, when the oedema combined with an already narrow airway can cause complete obstruction. Consider the use of an airway exchange catheter at extubation, and observe patient in a high dependency area for some time post extubation. In severe cases, a pre- operative tracheostomy may be required.

Answer 2

TFTTF

Regional anaesthesia in the form of neuraxial blocks or peripheral nerve blocks should always be considered as it avoids airway manipulation, provides good postoperative pain relief and reduces polypharmacy. However, regional and neuraxial blocks may be technically difficult due to spinal arthritis and loss of anatomical landmarks from contractures or deformities. LMAs and other supraglottic airway devices should be used where possible as they require minimal neck manipulation
for insertion and cause lesser trauma and subsequent laryngeal oedema compared with a tracheal tube. AFOI is the technique of choice in patients with an expected difficult airway or known cervical spine instability needing intubation. Cervical spine involvement is not always symptomatic.

Answer 3

FTTFT

The most common type of AAS is anterior AAS, occurring in 80% cases. Anterior AAS is worsened by flexion. Subluxation exists when the distance between the atlas and the odontoid peg exceeds 4 mm in patients older than 44 and 3 mm in younger patients; this can be diagnosed by plain radiography of the neck. Severe cervical spine instability may necessitate an AFOI or a tracheostomy under local anaesthesia for safe management of the airway.

REFERENCES AND FURTHER READING

  1. Samanta R, Shoukrey K, Griffiths R. Rheumatoid arthritis and anaesthesia. Anaesthesia. 2011; 66: 1146–59.
  2. Fombon FN, Thompson JP. Anaesthesia for the adult patient with rheumatoid arthritis. CEACCP. 2006; 6: 235–9.
  3. Keith Allman, Barry Baker, Iain Wilson. Anaesthesia for the patient with rheumatoid arthritis. Oxford Handbook of Anaesthesia 3rd edition. Oxford University Press (2011)
  4. Temprano K. Rheumatoid arthritis. Emedicine. http://emedicine.medscape.com/article/331715-overview
  5. Calder I. Airway management in cervical spine disease. In: Calder I, Pearce A, eds. Core Topics in Airway Management, 2nd edn. Cambridge: Cambridge University Press, 2010: 244–54.

APPENDIX 1

Perioperative steroid supplementation

Patients currently taking regular corticosteroids

  • <10mg / day of prednisolone or equivalent – assume normal HPA axis – no additional cover required
  • >10mg / day of prednisolone or equivalent o Minor surgery e.g. hernia – routine preoperative steroid or 25mg IV hydrocortisone
    at induction
    • Intermediate surgery e.g. hysterectomy – routine preoperative steroid plus 25mg IV hydrocortisone at induction, then 6 hourly for 24 hours.
    • Major surgery e.g. cardiac – routine preoperative steroids plus 25mg IV hydrocortisone at induction, then 6 hourly for 48-72 hours

Resume normal oral therapy when gastrointestinal function has returned.

Patients not currently on corticosteroid therapy

  • <3months since stopping steroids – Treat as if on steroids
  • >3 months since stopping steroids – No perioperative steroids necessary

Patients on high dose immunosuppression

  • Should continue usual immunosuppressive dose parenterally until able to revert to normal oral intake. For e.g. if a patient takes 60mgs of prednisolone / 24 hours, he/she should receive 240mgs of hydrocortisone / 24 hours until oral intake can be resumed.

Equivalent drug doses: 10mgs prednisolone=dexamethasone 1.5mgs=hydrocortisone
40mgs=methylprednisolone 8mgs=betamethasone 1.5mgs.

References:

Allman KG, Wilson IH (2011) The patient on steroids. Oxford Handbook of Anaesthesia. 3rd ed. London: Oxford University Press.

QUESTIONSA patient with long standing rheumatoid arthritis (RA) presents with hoarseness of voice. What are the anaesthetic implications of this? Choose the single best answer.This history is not significantHoarseness might worsen after endotracheal intubation-the patient should be warned about th...

This history is not significant Hoarseness might worsen after endotracheal intubation-the patient should be warned about this The patient may be difficult to intubate as the vocal cords may be swollen The patient probably has cricoarytenoid involvement, which combined with airway oedema post intubation can cause complete airway obstruction in the post operative period.. Regarding anaesthesia for patients with RA (true/false): Spinal and epidural anaesthesia should be used where possible Regional nerve blocks are contraindicated Awake fibreoptic intubation (AFOI) may be needed in cases of severe atlanto-axial subluxation An LMA can be used for airway management to limit neck manipulation Cervical spine involement in RA is always accompanied by symptoms. Regarding atlanto axial involvement in RA (true/false): The most common type of atlanto-axial subluxation (AAS) is posterior AAS Subluxation exists when the distance between the atlas and the odontoid peg exceeds 4 mm in patients older than 44 and 3 mm in younger patients Flexion of the neck is more harmful than extension AAS can be diagnosed only by a CT scan Severe AAS may necessitate an awake tracheostomy for airway management. The issues in airway management are the increased prevalence of a difficult airway (RA patients needing cervical spine surgery have a high prevalence of grade 3 or 4 laryngoscopy) and the presence of AAS, which may result in spinal cord injury during airway management.. Cervical spine X-rays in a patient with severe rheumatoid arthritis on long term steroids showing anterior atlanto-axial subluxation (with permission from Oxford University Press).. There is no one recommended anaesthetic technique; choice of technique will depend on the patient’s general condition, type of surgery, patient preference and skill of the anaesthetist.

ANAESTHESIA, SLEEP AND DYSSOMNIAS- PART 2 ANAESTHESIA TUTORIAL OF THE WEEK 269 : WFSA - Resources |

There is an autoimmune component to the disease c. Onset of narcolepsy is in late adulthood d. Narcolepsy is characterised by excessive sleepiness and cataplexy Regarding Restless legs syndrome; a.. There is no sex preponderance amongst suffers, but a strong genetic link.. Increased sensitivity to anaesthetic agents Delayed emergence from general anaesthesia Post-operative hypersomnia and apnoea Post-operative sleep paralysis Cataplexy during positioning for regional anaesthesia Interactions between treatments for narcolepsy and anaesthetic agents. These include Cheynes-Stokes breathing – central sleep apnoea (CSB-CSA), high altitude periodic breathing, idiopathic (primary) central sleep apnoea and central sleep apnoea due to other medical conditions.. Hypercapnic sleep apnoea’s occur in those that have an attenuated response to hypercapnia, such as those with chronic ventilatory failure.. Relevance to anaesthesia is both in the pathophysiological effects of the condition, and the effects of anaesthesia on the patient.. It has been shown that up to 10% of the population of the U.S suffer from RLS, and as many as 2% experience moderate or severe symptoms 8 .. The cardinal symptoms of idiopathic hypersomnia, in the absence of organic pathology, are non-imperative sleep, excessive daytime sleepiness, prolonged night time sleep, difficulty awakening, sleep drunkenness on waking (automatic behaviour, confusion, and repeated returns to sleep) and prominent mood disorders, such as depression.. Theoretical complications of general anaesthesia in a KLS patient include triggering a sleeping episode, increased sensitivity to anaesthetic agents, apnoeic episodes and prolonged extubation time.. Anaesthesia, analgesia and operative stress can all affect normal sleep patterns Anaesthetic management of patients with dyssomnias should involve a thorough pre-operative assessment, an anaesthetic technique designed to minimise effects on the disease process, and consideration of post-operative critical care management. Anaesthesia .2008; 63: 880-882.. Central sleep apnoea.

ACUTE PAIN MANAGEMENT PART 2 ASSESSMENT AND MANAGEMENT ANAESTHESIA TUTORIAL OF THE WEEK 295 : WFSA - Resources |

Poor recognition and management of acute pain occurs commonly Acute pain has no bearing on post-operative complications Pain increases anabolic hormone production The severity of acute post-operative pain may has been suggested as a risk factor for the development of chronic pain In general, pain causes an increase in parasympathetic nervous activity Nociception, and a patient’s perception of pain are the same thing If possible, pain should be assessed with the patient active Pain should be assessed regularly during treatment Patient comfort only relates to analgesia Adverse effects of analgesic drugs need not be monitored during treatment Intramuscular injection provides reliable drug absorption Continuous IV opioid infusion carries the highest risk of serious adverse effects Patient-controlled analgesia devices are only used to deliver opioid medication Multi-modal analgesia aims to reduce opioid doses and adverse effects Acute pain service teams have clinical responsibilities only. Several studies have shown that poor recognition of acute pain and inadequate pain management occurs commonly.. Explain the need for effective management of acute pain Describe the role and method of assessing acute pain Discuss modern analgesics and their application. These factors may impact upon the response to both pain and its treatment, and so should be considered when assessing and managing acute pain.. Last, but certainly not least, is the possible development of chronic pain, from the acute pain state.. Effective pain management in these patients may go some way toward guarding against the development of Persistent Post-Surgical Pain (PPSP).. Consideration of pain in terms of its nature and relationship to injury facilitates effective acute pain management.. An example would be a four-point scale containing the words ‘no pain’, ‘mild pain, moderate pain, and ‘severe pain’.. In order to deliver effective yet safe analgesia, any on-going assessment of pain should include the identification of adverse effects associated with the analgesic drugs employed.. Ketamine can be delivered via this route for treating procedural pain or acute pain in the emergency department.. It provides good analgesia for procedural pain and neuropathic pain and offers a useful adjunct or alternative to opioids when managing the opioid tolerant patient.. A role in acute pain management has been suggested from evidence of salmon calcitonin proving effective shown in the reduction of acute pain caused by osteoporotic related vertebral fractures.. These techniques are commonly employed for treating post-surgery pain, but also have a role for treating other forms of acute pain.. The recognition of the importance of good acute pain management has prompted the development of teams specialised at managing acute pain.. Such services have been shown to reduce pain scores and improve management of post-operative pain.

Journal Article•DOI: 10.3171/JNS.1988.69.6.0895•Transoral-transpharyngeal approach to the anterior craniocervical junction: Ten-year experience with 72 patients[...]Arnold H. Menezes1, John C. VanGilder•Institutions (1)01 Dec 1988-Journal of NeurosurgeryAbstract: The anterior transoral-transpharynge...

(Video) Approaches to ventral extradural pathologies of craniocervical junction with Dr. Jean-Paul Wolinsky. Rheumatoid arthritis of the cervical spine.. In patients who had paralysis due to atlanto-axial subluxation, no recovery occurred if the posterior atlanto-odontoid interval was less than ten millimeters, whereas recovery of at least one neurological class always occurred when the posterior atlanto-odontoid interval was at least ten millimeters.. In this series, although only patients who had a neurological deficit were operated on, we observed the range of the posterior atlanto-odontoid interval that was associated with poor or no recovery after the operation, and we identified the safe range on the basis of the patients in whom paralysis did not develop.. Eight patients (30%) had preoperative instability of the craniovertebral junction due solely to their pathology, 11 patients (40%) suffered instability after transoral surgery, and eight (30%) were without clinical or radiographic evidence of instability (mean follow-up period 14 months).. Craniovertebral junction instability predominated among patients with rheumatoid arthritis: 91% required fusion and 45% presented with pre-existing instability.. Topics:Chiari malformation(52%), Spinal fusion(52%), Clivus(50%)...read more. In patients who had paralysis due to atlanto-axial subluxation, no recovery occurred if the posterior atlanto-odontoid interval was less than ten millimeters, whereas recovery of at least one neurological class always occurred when the posterior atlanto-odontoid interval was at least ten millimeters.. All patients who had paralysis and a posterior atlanto-odontoid interval or diameter of the subaxial canal of fourteen millimeters had complete motor recovery after the operation... Eight patients (30%) had preoperative instability of the craniovertebral junction due solely to their pathology, 11 patients (40%) suffered instability after transoral surgery, and eight (30%) were without clinical or radiographic evidence of instability (mean follow-up period 14 months).. Craniovertebral junction instability predominated among patients with rheumatoid arthritis: 91% required fusion and 45% presented with pre-existing instability... Patients with irreducible subluxations or significant neurologic deficit may best be treated with anterior decompression and fusion alone or in concert with posterior fusion... Long-term incidence of subaxial cervical spine instability following cervical arthrodesis surgery in patients with rheumatoid arthritis.. Rheumatoid arthritis of the cervical spine.. Arthrodesis of the cervical spine in rheumatoid arthritis... In patients who had paralysis due to atlanto-axial subluxation, no recovery occurred if the posterior atlanto-odontoid interval was less than ten millimeters, whereas recovery of at least one neurological class always occurred when the posterior atlanto-odontoid interval was at least ten millimeters... In this series, although only patients who had a neurological deficit were operated on, we observed the range of the posterior atlanto-odontoid interval that was associated with poor or no recovery after the operation, and we identified the safe range on the basis of the patients in whom paralysis did not develop.. As the arthritis progressed, sometimes with acute inflammatory exacerbations, more joints became involved and, by the sixteenth to the twentieth weeks of the experiment, a progressive polyarthritis, with gross joint deformities and restricted function, developed in the majority of the limb joints..

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