BONUS CASE: A pain in the neck

Dr Roz Benson, consultant rheumatologist talks to Dr Nicholas Aquilina, a rheumatology trainee from Malta, about an unusual cause of neck pain which left undiagnosed can have serious sequela. 

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Transcript

 0:01
 You're listening to the Talking Rheumatology Spotlight podcast brought to you by the British Society for Rheumatology. Welcome to this Talking Rheumatology Spotlight podcast. I'm really delighted today to be joined by Nick Acquilina, who is a doctor working in Malta, and he's going to share with us a really interesting case. My name is Roz Benson, I'm one of the rheumatology consultant in Liverpool and I'm also one of the digital learning editors at the BSR.I'm going to hand over to you, Nick, to tell us a bit about your job and also a bit about what it's like working as a rheumatology trainee in Malta

 Yes, thank you for the introduction, Roz. So essentially for those who don't know, because a lot of people actually don't, Malta is a very small island nation in the middle of the Mediterranean Sea and we have a population of around 500,000 people.

 0:58
 Despite all of this, we only have a very, a very small number of practising rheumatologists and there are 6 consultants for that whole catchment area and there are also a number of resident specialists.

 1:10
 And in terms of trainees, unfortunately it's only me so far, but we do have some people interested in joining guard department.

 1:18
 In terms of the situation, I think it brings a unique sort of flavour to how rheumatologies view than to how we practise it because most of the times we're very limited in the resources we have compared to your centres.

 1:33
 And it's makes us a bit more creative sometimes, which is what we're going to see in this case as well.

 1:39
 That's a really nice lead in to this interesting case you're going to tell us about.

 1:43
 So thank you for that bit of background.

 1:46
 And then so to start off with, can you tell us a bit about the age of the patient and how they initially presented to hospital?

 1:52
 Yes, of course.

 1:53
 So as a prelude to all of this, yes, you are listening to a rheumatology podcast.

 1:59
 It's not a neurology one because the symptoms might be a bit confusing.

 2:03
 So we are going to discuss the case of a 57 year old gentleman who was previously healthy and not known to suffer from any comorbidities with no significant family history.

 2:15
 He woke up in the in the early hours of the morning at like 3:00 AM few months ago with severe occipital and cervical pain which was also associated with chills and rigours and in fact he was found to have a temperature of 38.3°C.

 2:31
 When he experienced these symptoms, his wife called the ambulance and he was brought to our local emergency department.

 2:38
 We have one main emergency department though there are some small private ones.

 2:44
 So it was brought to the acute General Hospital and on review the patient denied the symptoms of photophobia and phonophobia.

 2:53
 So even though there weren't like meningitic signs, symptoms per SE, he was still experiencing this neck pain and most of the time would think meningitis with such a presentation, Right.

 3:04
 Lots of red flags there.

 3:05
 Fever, sudden onset headache, sort of neck pain.

 3:08
 Yeah.

 3:09
 I'd be worried if I was the Med Reg seeing this patient.

 3:12
 Yes.

 3:12
 Unfortunately in our healthcare system it doesn't work like that.

 3:16
 So the no Med Reg actually saw the patient.

 3:20
 But So what happens is that the patient is triage at casualty and then the emergency doctors, the physicians worked them up themselves first.

 3:30
 So given the symptomatology, he underwent a complex neurological examination which surprisingly revealed the sensory motor deficits in both the upper and lower limbs in a symmetrical manner.

 3:43
 And it was an upper motor neuron pattern of loss.

 3:46
 So it was hyperreflexic for example, and one wouldn't expect someone with meningitis to have any sort of deficit like that.

 3:54
 So that baffles them a bit.

 3:57
 So they went down the part of requesting certain investigations.

 4:01
 The patient himself mainly also had severe, severe stiffness of neck movements, flexion of the neck especially cause severe intense stroke like sensations down his spine.

 4:13
 And aside from that, he denied any trauma, which is also very pertinent to the, to the case.

 4:19
 So really going from a very fit well man suddenly to be extremely disabled with this severe neck pain and fever.

 4:27
 It's quite a change really even 24 hours for him.

 4:29
 Yes.

 4:30
 So it sounds like a very good neurological examination was performed by the admitting team or by the the emergency physicians.

 4:38
 What were some of the initial investigations that were performed?

 4:42
 So initially the patient has his blood test taken and before he was seen by the emergency physicians.

 4:48
 So by the time they reviewed him, they had some haematological and biochemical results.

 4:54
 He was found to have a neutrophilia with a neutrophil count of around 21 x 10 to the power of 9 per litre was quite significant and that made them think of bacterial meningitis as a possibility.

 5:07
 He also had a very, very high CRP.

 5:10
 It was in the range of like 360, two, 170 milligrammes per just per litre.

 5:15
 So was quite, quite elevated.

 5:16
 And given the fever, the symptoms sort of, they weren't expecting that there was anything else from meningitis or an Abscess perhaps which can cause the neurological compromise.

 5:28
 And then he underwent a city scan of the head, which in the emergency department is very, very easy to organise was they literally don't even have to vet it.

 5:37
 And the city was unremarkable for any accesses or collections anywhere.

 5:43
 But it did report, the radiologist did report that there were calcifications around the sea to vertebra and the death.

 5:52
 So when I don't know about you, but when I see classification on the city and it's an accurate situation, I tend to go ignore it sort of.

 6:00
 I don't really, you know, give it importance.

 6:04
 That was exactly what my thing could be.

 6:06
 I think it'd be very easy to in this situation to be quite tunnel visioned, wouldn't you, with this sort of patient in front of you to not give that bit of the CT report much attention?

 6:16
 Yes, and that comes also from a lack of awareness about certain conditions as well, which will be seen.

 6:21
 In fact, the neurosurgeons were consulted because the the protocol in our hospital is that if the patient has folk in neurological science with fever and exifanous, even even until meningitis is actually proven, they should be reviewed by the neurosurgeons and an MRI of the cervical spine would have to be ordered.

 6:42
 And it's the only time an MRI is done from an urgency in our country.

 6:47
 And the MRI was done in the early hours of the morning and it showed that the patient had soft tissue expansion and what was referred to as panmous formation around the dents.

 6:58
 So at this point, had he been started on any treatment whilst these scans and that sort of thing were awaited?

 7:03
 So while everyone was waiting for the results, what actually happened was that the patient was in the meantime admitted to the neurosurgical ward where he had a lumbar puncture and the lumbar puncture showed that he had no evidence of meningitis on a rapid screen.

 7:19
 Our local rapid screen screens for the most common types, so mainly the viral ones and the main bacterial ones like Nicaea, the iron strep.

 7:27
 Additionally, the CSF analysis was quite, quite unremarkable.

 7:31
 There was nothing on the gramme stain.

 7:33
 There was nothing in terms of biochemistry.

 7:36
 So whatever they were dealing with at that point in time confused them because they were thinking it was an atypical presentation of a typical disease like meningocephalitis or an abscess.

 7:48
 But when they saw the report of the MRI and they saw the word pannus, they immediately thought rheumatology, which is why they called us.

 7:57
 Well, that makes a lot of sense.

 7:58
 I mean that was yeah.

 8:00
 So I guess along the way that this important investigations to thinking about what are this of urgent conditions that we need to rule out were carried out with the blood tests.

 8:10
 And then thinking about the lumbar puncture, I guess anisochromia was found as well.

 8:14
 Because I think with a sudden onset headache you need to think about subarachnoid haemorrhage as well, don't you?

 8:19
 Yes.

 8:19
 To be fair, it was only a few hours after the presentation.

 8:22
 So the headache started at 3:00 AM became like 4-5 ish and developer puncture was and it's around 8:30-ish.

 8:29
 So 12 hours for the example from I think.

 8:31
 I didn't really pass as such but.

 8:34
 And yeah, there was no evidence of haemorrhage either.

 8:38
 And so then quite quickly these radiological investigations being performed.

 8:41
 But yeah, it's still a bit of a quandary as to what this might be.

8:51
 As a rheumatology team, I would not quite know what to do with this.

 8:55
 So what, what did you do?

 8:56
 So we were biassed because we did have two similar cases in the pre preceding months.

 9:01
 You know what happens?

 9:02
 Like sometimes you don't see something for like a million years and then suddenly you see like all of it, this sort of like 3 weeks.

 9:08
 It's crazy.

 9:08
 Sometimes in the UK we say you wait for a bus for ages and they all come along at once.

 9:13
 Yes, you say that too in Malta too, in a different way but on the same wavelength, sort of.

 9:18
 So, yeah.

 9:19
 So when they called us, I remembered the neurosurgery registrar told me, listen, what?I'm just calling you as a courtesy just to ask what investigations we need to take for this patient in terms of a rheumatological screen, which is something that irks me a bit because there's no such thing as a remote relations screen. And I have opened his scans and I was, to be fair, quite a bit surprised because even though we do sometimes see calcification in that area, especially after trauma, and this patient had no history of trauma

 10:00
 So I told her to start, listen, I do believe that this is not RA because there are no erosions and the patient does not have any other joints involved.

 10:09
 It's quite atypical.

 10:10
 It would, you know, it wouldn't be the first on my differential list.

 10:14
 They did tell him, listen, we have had cases in the past of something called crowned dens syndrome and he was like, what is that?

 10:23
 So we did consider it as our top differential, but the patient either way still needed urgent surgery because his motor weakness worsened.

 10:32
 He was unable to get out of bed on his own.

 10:34
 But part of differential being condensed and wrong, we went down the route of excluding inflammatory arthropathies either way.

 10:40
 So we did check his rheumatoid factor and TCP and they they were all negative.

 10:45
 And we also checked his uric acid which was normal.

 10:48
 I mean, even though that doesn't exclude gout per SE, the patient had no real risk factors for it anyway.

 10:54
 And and no previous history of any joint involvement in a what in place that might suggest the history of gout exactly.

 11:01
 Yeah.

 11:01
 So you've had a diagnosis there of crowned dens syndrome and you've explained this to neurosurgeons.

 11:08
 Were they a bit flummoxed by that?

 11:09
 What do they think we should do next?

 11:11
 You've got somebody with pending significant neurological impairment as a result of their symptoms and signs.

 11:18
 So what?

 11:18
 What?

 11:19
 What do they want to do and what did you do?

 11:21
 So in reality, coincidentally, the same neurosurgical team taking care of this patient had a consultant in it who had dealt with a case jointly with us just a few months back.

 11:32
 And this patient had no neurological compromise and she actually recovered spontaneously without treatment by the time they had discussed the case with an external consultant.

 11:43
 So when we mentioned that, they said, but it's not like the other patients.

 11:47
 So why are you saying it's that?

 11:49
 So in reality we said, listen, the radiological findings are quite characteristic if you want to go ahead with surgery.

 11:59
 They actually performed the compression surgery and we have no objections.

 12:04
 We advise them to send the tissue for Histology, which they did.

 12:08
 And we still initiated treatment with corticosteroids and colchicine.

 12:14
 And did the Histology show anything when they sent it to interestingly enough, it was all the actual actually the histopathologist said that people this is just a hunk of crystal.

 12:26
 It was calcium pyrophosphate

 12:28
 And so they had this lot so part of the synovia was indeed removed.

 12:44
 To my knowledge.

 12:45
 That's what they did.

 12:46
 I'm sure they did a million other things.

12:50
 But the patient definitely needed it because of course myelopathy can rapidly to paralysis and the trapezia absolutely so.

 12:59
 And then postoperatively, how did the patient do sort of within the first few days and then how how are they doing now?

 13:06
 So we had started Prednisolone at a dose of 40 milligrammes every day and initially we gave him a large dose of 1 milligramme per kilogramme, which was around 60 and then we put it down to 40 and we gave him colchicine 0.5 milligrammes 3 times a day.

 13:22
 So the rationale behind that was that there is very, very limited evidence out there with regards to the management of crowned dens and there has only, there have only been like a small handful of studies about the management of Calcium pyrophosphate deposition disease in general.

 13:40
 So the way we went about it was that if this if this is a severe case, we should just sort of give everything we have available.

 13:49
 And the patient actually did start to improve immediately after the operation and also with the treatment because in fact he started rehabilitation whilst in hospital.

 14:01
 He was able to walk and ambulate on his own, but his fine motor skills were still were still a bit weak.

 14:08
 So he ended up being transferred to a rehabilitation hospital and he ended up doing very well.

 14:14
 And in fact I've seen him recently and he's completely recovered.

 14:18
 But the problem I have now is we don't know exactly what we're going to do in terms of sequential follow up.

 14:27
 So yeah, quite challenging really, isn't it?

 14:30
 And is he still on any treatment now?

 14:33
 Are you giving him colchicine or anything like that?

 14:35
 So initially we had attempted to follow the trial findings.

 14:41
 So I read that around two years ago in France a trial was carried out with regards to polycin and Prednisolone use in calcium pyrophosphate deposition disease.

 14:51
 And with all its limitations and the the fact that the cohort was possibly not well selected, it did show that technically both Prednisolone and cognacine given for a very short duration would have the same effect.

 15:05
 So we initially gave him the treatment for two weeks, but when we stopped the treatment, he immediately started experiencing a recurrence of symptoms.

 15:15
 So he was already improving with rehabilitation.

 15:18
 And the physiotherapist pointed out that listen, he's dragging his leg again, wasn't doing that.

 15:25
 And then we restarted it and gave him an 8 week course of a tapering dose of Prednisolone with the same dose of colchicine.

 15:34
 And then we stopped it and so far it's OK.

 15:37
 Did he have any recurrence of neck pain at that time when he had the weakness in the leg noted?

 15:43
 So he did not claim that he had recurrence of neck pain.

 15:47
 But when the neurosurgeons examined him, he did have reduced movement of his neck compared to the previous examination.

 15:55
 In fact, it coincided with the removal of his seal chairs and the wound had healed very, very nicely.

 16:02
 So they, they weren't blaming that.

 16:08
 So this is, I mean, he's said previously that sometimes you see in this cohort that they might have had a history of trauma.

 16:14
 So is there a typical patient that we should consider this condition in or actually is it just a bit of a surprise when it happens and we just need to be aware of it?

 16:24
 So basically, literature reviews have described ground and syndrome as being common air in elderly females, so females over the age of 60, which makes this an atypical case because he's a male under the age of 60.

 16:38
 And it's also associated with two major groups of conditions, First of all traumatic conditions.

 16:45
 I remember I had one case where a patient fell in hospital, which is one of the big no nose of medicine and he sustained a quite, quite a nasty head injury and he developed fever, a high CRP.

 16:57
 Everyone thought it was sepsis from a hospital acquired source.

 17:01
 And the CT actually showed crowned dense.

 17:04
 And the other case was where a metal sheet fell on her head. So they were both traumatic and in fact you know in the Cochrane database, there's nothing about a traumatic crowned dens, it's just that it exists.

 17:22
 The other association is with metabolic disorders.

 17:25
 So in fact this patient was screened for diabetes.

 17:28
 It was also screened for hemochromatosis, but the screens were were negative.

 17:35
 Any condition which can increase the concentration of inorganic phosphates and pyrophosphates inside the cell can technically trigger calcium pyrophosphate deposition disease.

 17:44
 So we also checked his calcium, his parathyroid hormone levels and they were all normal.

 17:50
 And it makes sense really, doesn't it, this idea of potentially trauma and then the collection of their calcium pyrophosphate crystals.

 17:57
 We see this in areas of damaged joints, don't we?

 18:00
 So osteoarthritis in the knee and then you get a pseudogout flare up potentially in the knee.

 18:05
 So it's just that it's in a more unusual anatomical location, isn't it?

 18:09
 Potentially with more significant as a result.

 18:12
 Yes.

 18:13
 And in fact, to be fair, anatomically it does sort of make sense.

 18:17
 I believe I read a study once saying that it was an ultrasound guided study where they grabbed a cohort of CPPD patients and they all had an ultrasound of their knee and the majority of the the patients had calcium pyrophosphate.

 18:35
 The positions, you know ultrasonography in the fibrocartilage, not the hyaline cartilage components.

 18:42
 So if you have to look at crowned dens syndrome in general, as you know it affects the transverse, the cruciate and the A layer ligaments around the dense and those are all made of fibrocartilage, not hyaline cartilage.

 18:56
 So perhaps the predilection for that site in particular, not not other spinal ligaments as in other conditions like DISH, could be explained by that.

 19:07
 No one knows exactly why, but scientists have shown that calcium pyrophosphate crystals in in particular have a tendency to cluster inside extracellular matrices rather than like uric acid crystals.

 19:22
 And in fact, it's a whole inflammasome path waiting.

 19:25
 So it does make sense when you look at the micro, the molecular biology of it.

 19:30
 That's really interesting.

 19:31
 And so I guess the other thing from this is that you have one patient who has spontaneously improved and with no treatment required and then a very different treatment pathway required for the second patient you described.

 19:44
 I think you said that you've had three patients with this condition.

 19:47
 That other patient, how did they do?

 19:49
 Did they require treatment?

 19:51
 So the patient who had the metal sheet fall on her head received no treatment.

 19:56
 She recovered spontaneously.

 19:59
 The patient who fell in hospital received colchicine.

 20:03
 And in this case, I think it was the only relapsing case out of the three that we had.

 20:09
 But the problem is we have no idea how we're going to follow him up because calcifications will persist on SAT.

 20:15
 They won't disappear.

 20:17
 And even when we have a CPPD flare of the knee, just because we injected the knee or we treat the patient with colchicine or prednisolone.

 20:26
 The calcification still persists on X-ray, so that's a challenge in itself.

 20:32
 But I would say if the patient have had a recurrence of neck pain, the the first thing we're going to do is suspect that has a relapse.

 20:40
 But there are 1,000,000 causes of neck pain.

 20:42
 So how are we going to differentiate between them?

 20:47
 Yeah, yeah, absolutely.

 20:48
 And I guess there will be perhaps you picked pieces of the history that the rapidity of the onset of the neck pain, which was the case in this this situation and then the fever, the systemically being unwell, which is something that you often often see for crystal arthropathy.

 21:04
 Don't you might all be pointers.

 21:06
 But yeah, absolutely, there's a lot of other things that you need to consider as part of your differential.

 21:10
 So this is going to be challenging, not only challenging with the initial presentation and treatment, but really future management for this matter. Most of the studies which exist are very, very small, so they're prone to bias.

 21:28
I believe even 1 publication only contains 10 patients and a third of them that's not exactly so you can imagine, but the the actually the theme right with the best in inverted commas evidence is hydroxychloroquine because it was the only one to speed the the outcomes of the patient.

 21:52
 So and the recovery of the patient in fact and methotrexate was not found to be helpful in two studies and there are some studies looking at the use of interleukin 1 and interleukin 6 inhibition.

 22:05
 The reason is because as we're saying, the crisis trigger and flamizone response just like pyrin and FMF.

 22:12
 So logically one would try to give an interlocking 1 inhibitor in this case.

 22:17
 Of course, the issue with that is sourcing it and getting it approved.

 22:22
 And in the Malta, Anakinira is often out of stock

 22:27
 So yeah, yeah, absolutely.

 22:28
 So I guess so.

 22:29
 So time will tell how he does with the ongoing culture scene and then as you wean it off and whether, whether other sort of more adventurous treatment options need to be explored.

 22:39
 But hopefully this way, hopefully we don't, we won't need to, but who knows.

 22:45
 Thank you.

 22:45
 That's been really fascinating, OK, Something that I think we all need to be aware of and mindful of actually as somebody who presents some acute neck pain, are there any, I have a couple of key learning points in this, having never seen a patient with this case in my practise so far.

 23:00
 But do you, do you have anything that you would want to have any key learning points you would want to share from your experience?

 23:07
 Yes.

 23:07
 So I think the most important who were learning points I would share would be that first of all the early involvement of the rheumatology team is paramount.

 23:18
 And that's actually much more difficult than it sounds.

 23:23
 And I'm sure you know even in other rheumatological conditions in general we get patients referred to as very late, so early referral and recognition of the disease.

 23:32
 So the finding of calcification in that patient with a headache around and the calcifications being around the odontoid process should prompt immediate referrals.

 23:42
 So perhaps we can raise awareness even locally in our centre by having more multi disciplinary in discussions because I think that's how we learn from each other.

 23:53
 The second take home message from my end would be that the progress of the disease is nonlinear and there's not a lot of evidence to go off on.

 24:02
 However, using Prednisone and colchicine does help the patient.

 24:09
 So rather than waiting for a spontaneous resolution, especially if you have neurological compromise, this would be the initial treatment strategy of choice.

 24:20
 Yeah, no, that's really useful.

 24:21
 I think for me, the consideration of this in a patient who's had, I know this was a case of someone who was a traumatic and it was quite an atypical presentation.

 24:30
 But in someone who has had trauma and then this sudden onset of neck pain, there's no obvious Bony injury.

 24:38
 We need to consider this potentially.

 24:41
 I think the other thing for me which is helpful, a helpful reminder is that when we look at a scan or imaging that we've often performed imaging for a particular for a reason.

 24:51
 And as was evidenced in this.

 24:53
 But actually to be aware of the atypical sort of incidental, well, incidental and inverted commas findings that you might get on the scan.

 25:00
 And actually even if you don't understand them, to explore what that might be because actually that might clinch the diagnosis for you.

 25:07
 So I think that was a really interesting part of this story.

 25:11
 Yes.

 25:11
 In fact, I mean, technically, let's hypothesise that this patient was seen by an emergency physician who actually knew what crowded dens is.

 25:20
 That might have saved him from getting a lumber puncture, which was extremely traumatic for him as well.

 25:26
 So it might have bought some time, saved some investigations, although you might be quite a brave emergency physician not to do a number punctures.

 25:35
 They are always there because they're not the ones to do with them because we have to do with them.

 25:52
And I guess also if he has further presentations which are quite similar, it might be that it might, if there is a really strong feeling this is a repeated episode of crowned dens that actually a lumbar puncture isn't required because this could be quite unpleasant for him if he, I would image him of course.

So I would repeat the imaging, but I would not repeat the lumbar puncture, of course.

26:22
 No, that's really interesting.

 26:23
 Well, thank you very much for talking.

 26:25
 Thank you for inviting me.

 26:26
 It was super, super interesting.

 26:28
 That's been great.

 26:33
 Thank you for listening to Talking Rheumatology Spotlight brought to you by BSR.

 26:37
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