I first met this patient last year when I was in my surgical rotation.* At first glance, I couldn't believe she was experiencing one of the things in life that you only miss when it's gone - going to the toilet.
I now take you back to that afternoon, when we were clerking patients in the general surgical ward, where there was a grand assortment of cases. We already clerked a patient with stage four (metastatic) transitional cell carcinoma of the urinary bladder, as well as a patient with chronic urinary retention owing to metastatic prostatic cancer. It's rather sobering for me to witness so many oncological cases on one single day. It frightened me so much to witness death in operation - how its fangs were sinking deeper and deeper into the neck arteries of these poor wretches. Usually, in the wards, we moved in a group so that it was easier for everyone to proffer their opinions on individual cases. It also ensured that we learnt everything we had to during that session. It would not be as efficacious should we divide cases amongst ourselves and deal with them single-handedly (the majority opinion - as an independent introvert, I did prefer going on my own to tackle a case since I ardently believe it's the only way I can learn as a medical professional who assumes professional responsibility). Anyway, so that afternoon, the others crammed into the room with a patient afflicted by recurrent urinary tract infections and I went to this patient.**
Emma (fake name) did not look particularly unusual. In fact, you might even mistake her as one of the relatives of the patients in the ward. She looked healthy and lively. Conversant in many topics and cheerful, she was one of the rare patients in the ward who weren't daunted by the prospect of being harangued by a crowd of bumblebees desperate to feed. Her case was also rather strange, in that the sole, initial, identifiable symptom was the inability to urinate. Of course, this could point us to a few broad categories. However, in essence, not enough clues were provided from the outset. This necessitated a longer process of history-taking to elicit clues which could shed an inkling to her condition. Just like the last article, I've decided to switch to a more user-friendly format. In this case, it means putting all the information I gathered in the form of a list, just like how medics usually take clinical history. Just to clarify, I prefer using the present tense (simple) when describing clinical cases since we are, after all, dealing with representations and facts.
Patient Factsheet - History-taking:
Chief Particulars: 50 year old female, post-menopausal, G1P1; homemaker;
Chief Complaint and Characteristics:
(a) The inability to void urine (i.e. urinate) for the past sixteen hours (persistent, no sign of improvement in the interim); This is the reason why the patient, out of fear, presents to the A&E department of the hospital;
(b) Acute onset; single episode; patient fails to recognise any previous episode of difficulty of urination;
(c) The character of the inability to void can be better described as the lack of control - the patient is unable to initiate the process, rather than that the patient encounters a point of obstruction during an attempted incident of urination; even so, we are determined not to take the patient's word for granted. We are not ruling out anything at this stage;
(d) No associated symptoms with the acute urinary retention (as alleged); prior to that, there had been no urinary tract symptoms. This includes dysuria, haematuria, frothy urine, loin pain and abdominal pain.
(e) Review of Systems:
- No constitutional symptoms and no anaemic symptoms.
- Abdominal straining and bloating upon presentation due to the excessive retention of urine (however, that has since been resolved after admission);
- Bilateral lower limb numbness which has occurred for the past six days. It is progressively worse and involves the distal regions of the feet. It extends proximally (in the direction of the ankle). Moreover, she complains of gait disturbance, i.e. she cannot walk properly. This is mainly attributed to both the numbness and a 'slight tingling sensation' (paraesthesia) which arises from the peripheral regions of the lower limbs. These have also arisen for the past six days and gone progressively debilitating.
- No other reported symptoms, especially the gastrointestinal system.
(g) Treatment so far: Insertion of a Foley Catheter (unit: French) to relieve the straining of the urinary bladder by removing urine; investigations also underway.
Image of Foley Catheter (extracted from: https://cdns.webareacontrol.com/prodimages/1000-X-1000/7/L/7320164949Medline-Two-Way-Silicone-Elastomer-Coated-Coude-Tip-Latex-Foley-Catheter-L-L.png)
Past Medical (including autoimmunity) History:
- Suffered from upper lobe pneumonia for 2 weeks, where the patient finished the course of antibiotics a week before the index event, i.e. acute urinary retention;
- Asthmatic when young, although unable to recall the exact period of diagnosis; alleged that asthmatic symptoms have disappeared upon reaching adulthood, where the patient no longer requires the administration of inhalers;
- Treated for contact dermatitis 3 months ago, where the trigger was identified as a new type of fragrance the patient during the same period of time. The patient recovered after a course of topical steroids and avoided exposure to that particular product ever since.
Past Surgical History: Unremarkable.
Past Obstetric and Gynaecological History:
- Gravida 1, Para 1 (meaning that the patient has had one pregnancy and one delivery);
- Post-menopausal;
- Unremarkable with regard to the delivery and pregnancy; the foetus was delivered vaginally 20 years ago, with no identifiable post-operative and peri-operative complications;
- No gynaecological symptoms, such as abnormal vaginal discharge or per vaginal bleeding.
Drug History: currently undertaking topical Hormonal Replacement Therapy (HRT; oestradiol) for the treatment of post-menopausal symptoms, principally vaginal dryness, vaginal itchiness and dyspareunia (pain during sexual intercourse). Otherwise, no other form of medication taken chronically; no identifiable drug allergies; no recreational drug use.
Family History: Mother currently treated for lupus nephritis; first diagnosed with lupus (full name: systemic lupus erythematosus) thirty years ago and underwent long-term hydroxychloroquine therapy; Otherwise unremarkable;
Social History: Occasional smoker (1 cigarette per week for the past 20 years), non-drinker, living with husband and son; no identifiable life stressors requiring essential medical/psychiatric attention;
Infectious and Sexual History: Unremarkable; the patient also has no recent travel history. No other member within the same household presents with the same symptoms. The patient is not sexually active for the past year and does not have any identifiable history of sexually-transmitted infections.
Dietary History: unremarkable.
With all the information gathered, we can identify two principle issues - (1) acute urinary retention currently relieved by catheterisation, and (2) lower limb neurological symptoms. We are quite worried with (2) at this stage. Moreover, (1) necessitates further intervention and investigation. We cannot leave the Foley catheter hanging for the rest of the patient's life. Identification of the root cause is required for definitive treatment. At this point, before we perform any physical examination or investigation, I want to highlight six main directions to go for amidst a case of acute urinary retention:
Urinary Tract (Obstructive): The premise here is the presence of a lesion along/outside the urinary tract which impinges upon the normal conduit for urinary flow. This includes conditions such as foreign bodies and urinary tract stones (usually calcium-containing, or struvite - infectious);
Neuromuscular (Lack of Initiation): the nerves and/or muscles are affected. Since micturition (aka urination) requires neuromuscular control, once any of the components affected is affected, it easily leads to urinary retention. The defect can occur in either: (1) brain, (2) spinal cord, and/or (3) nerves. There are also myriads of differential diagnoses under each one, so we need to be careful and see if it fits in the bigger picture. Sometimes, instead of either structure, the one that bridges the two, the neuromuscular junctions, get affected. There is a condition called Myasthenia Gravis, an autoimmune disorder, where the accumulation of antibodies over the neuromuscular junction has rendered it very difficult for neural signals to be translated into muscle movement.
Inflammation/Infection (systemic or localised): this is applicable to both localised and generalised infections. Localised infections include a wide range of urinary tract infections, such as cystitis, pyelonephritis and candidiasis. Vulvovaginitis (since this is a female patient) can also be caused by microbes like Gardnerella vaginosis and Trichomonas vaginalis. For generalised infections, meaning that they affect multiple body systems, are usually not the main reason behind acute urinary retention when they're in rage. It is usually when they've simmered down, leaving behind some of their genetic material, that a phenomenon called 'molecular mimicry' arises. This phenomenon means that the immune system can see strands of similarities in genetic material/proteins between human cells and microbial cells. This leads to a gross autoimmune attack which can manifest in different forms. Such inflammatory and infective processes can lead to urinary retention in a variety of ways. The most prominent of which is the attack on the nerve endings and muscles involved in micturition. Since infections entail inflammation and calcification, urinary tract stones can arise. There is a type of stone called 'staghorn calculus' which is attributable to recurrent urinary tract infections. This leads to the obstruction of the urinary tract, preventing micturition.
Drug Use: Numerous drugs can give rise to this situation - they are concerned with neurotransmission. This can include anti-psychotics, tricyclic antidepressants (where they act through multiple pathways), antihistamines and anti-cholinergics. The parasympathetic nervous system is responsible for controlling urinary outflow (where the detrusor muscle of the urinary bladder contracts and the internal urethral sphincter, under involuntary control relaxes when stimulated). Any pharmaceutical regimen which dampens it, through the decrease in acetylcholine production and/or release, leads to urinary retention.
Iatrogenic: previous surgery which has inflicted trauma over the urinary tract; this can include previous catheterisation. However, from the patient's history, this is the index event. There are no identifiable, previous incidents of acute urinary retention. It is thus unlikely for the patient to have received catheterisation before. Also, the patient's surgical history is unremarkable. This renders an iatrogenic aetiology much less likely.
Idiopathic (meaning that we just don't know what happened), Psychogenic (where it is a psychosomatic symptom; patients benefit more from cognitive behavioural therapy than medical regimens): This is the last resort so I'll put them aside for now.
Drawing a line here, pelvic organ prolapse as elucidated in one of my previous articles can also cause urinary retention or incontinence. It really depends on the actual mode of presentation, since if the urinary bladder prolapses, urinary retention is caused instead. However, it is usually a chronic instead of an acute process.
Diagram illustrating some sites that stones can occur in the urinary tract and how this relates to obstruction, thus urinary retention (extracted from: https://healthjade.com/wp-content/uploads/2017/08/kidney-stone-remedy.jpg)
Physical Examination:
Neurological Examination (Upper Limbs, Lower Limbs, Cranial Nerves) - assessment also includes examination of gait (i.e. walking);
Abdominal Examination + Digital Rectal Examination;
Significant findings are recorded as follows:
(a) Identification of a Foley Catheter with normal urinary output (in terms of clarity and character; not frothy, no visible haematuria); No abnormalities associated with the kidneys and urinary bladder; Anal reflex, which is carried out by nerve endings S3-S4, is lost.
The bulbospongiosus reflex is not tested. It utilises S2-S4 of the spinal cord, where it involves the tugging of the Foley Catheter (or in other patients, stimulating the glans clitoris in females, or glans penis in males) while assessing the presence/any abnormalities pertinent to the anal sphincter tone. Normally, if the anal reflex is deficient, the bulbospongiosus reflex is expected, as well, to be impaired.
(b) A singular linear scar (~5 cm) located over the lateral aspect of the left leg, attributable to previous trauma (gait unsteadiness); stocking distribution of partial sensation loss (both pain and vibration) involving L4, L5 and S1 bilaterally; bilateral weakness (3/5) in ankle plantarflexion, ankle dorsiflexion and extension of the great toe; less serious weakness in hip flexion and knee extension (4/5) (involving L2-L3); diminished ankle and plantar reflexes bilaterally; struggles to carry out heel-shin test bilaterally (postulated to be a sensory problem, rather than an issue with coordination); Babinski's Sign negative and no issue with tone.
(c) The patient's gait is unsteady, with abnormal heel-strike bilaterally. Romberg test negative;
(d) No abnormalities detected in the upper limbs and cranial nerves.
From the aforementioned results, it is more suggestive of a neurological condition than a urinary tract one. This is also consistent with the patient's claim that the inability to urinate is associated with the wanting of capacity to initiate the process, instead of the presence of a distal obstruction. We hence carry out the following investigations:
Investigations:
Wholesale of general tests, including Full Blood Count (FBC), Coagulation Profile, Liver and Renal Function Tests, U&E, ESR and CRP;
Lumbar Puncture (where we want to see what exactly happened to the spinal cord and nerve endings there);
Nerve Conduction Studies (of the lower limbs, so as to assess general functioning);
Exclusion of other possibilities, such as HSV serology, HIV serology and VDRL (testing for neurosyphilis).
Spirometry is only performed if the patient reports of breathlessness and low blood oxygen levels. This is a possibility since, if the patient truly has a neuroinflammatory disorder, it is likely to spread to nerves elsewhere.
The cerebrospinal fluid (CSF) obtained from Lumbar Puncture is going to be tested for several big parameters:
(a) Protein Levels (as compared to blood);
(b) Glucose Levels (as compared to blood);
(c) Cell Count (Microscopy);
(d) Predominant White Blood Cell type;
(e) HSV DNA (through PCR), HIV antibodies and VDRL for the screening of sexually-transmitted infections;
[8] Diagram showing two scenarios in nerve conduction studies (normal and abnormal, e.g. demyelination in multiple sclerosis). Demyelination occurs in diseases such as multiple sclerosis and Guillain-Barré Syndrome. This leads to slowing of neurotransmission and deficiencies in sensory and motor functions, as well as reflexes.
Diagram showing how a lumbar puncture is performed in two different positions. I would say that the lying position is what we prefer, with the patient assuming a lateral decubitus position. A needle is inserted over L2-L3, where we can avoid the risk of damaging the main body of the spinal cord. At around L2, a point called the conus medullaris is reached, where it gives way to a bunch of nerve endings called the 'cauda equina'. These nerve endings float around the CSF and when the needle gets in, they can move swiftly away. The lower risk of damage also means that the patient endures lower risk of permanent motor and sensory impairment after the procedure. Diagram extracted from: https://nursingcrib.com/wp-content/uploads/2015/09/Blausen_0617_LumbarPuncture.png.
Diagram showing the anatomical positions of the conus medullaris and cauda equina. We aim to reach the cauda equina and avoid the conus medullaris and the main body of the spinal cord above. Diagram extracted from: https://i.pinimg.com/originals/db/1e/7b/db1e7b2019be399b57c78c2fea3d769a.jpg.
Results of Investigations: [Summary]
Slowed nerve conduction over the lower limbs;
CSF showing heightened protein and reduced glucose as compared to blood, with high concentrations of lymphocytes;
CSF negative for all other tests performed, including antibody and PCR tests for sexually-transmitted infections;
Heightened ALT and AST on Liver Function Tests;
Raised inflammatory markers in blood, i.e. ESR and CRP;
Lymphocytosis in blood.
We have decided not to perform specific autoimmune antibody tests in blood. Gathering such results, it is very likely that the patient has a neurological disorder called Guillain-Barre Syndrome.
It encompasses a broad spectrum of conditions, including various subtypes which can be characterised by their onset, progression and anatomical involvement. Approximately 100,000 people develop this condition worldwide every year. We suspect that the patient suffers from a paraparetic subtype, where both lower limbs are affected. There are also signs of impact over the lumbosacral plexus, which contains nerve endings S2-S4 supplying the bladder. This also explains why the anal reflex, involving the external anal sphincter (which is under voluntary control) is lost. The patient's lack of bowel symptoms can be attributed to the fact that the patient has not eaten for the twenty hours prior to admission. We believe that the trigger is the previous infection (pneumonia), leading to hyperactivation of the immune system. Regarding the patient's autoimmune history (contact dermatitis and childhood asthma) and family history (mother afflicted by lupus), there is a high possibility that the patient also experiences a higher tendency for autoimmune reactions.
Diagram showing the extents of anatomical involvement for different subtypes of Guillain-Barré Syndrome (extracted from: https://pn.bmj.com/content/practneurol/15/2/90/F1.large.jpg?width=800&height=600&carousel=1).
After making the diagnosis, we have decided to initiate treatment straight away since this disease can progress quite rapidly. We perform the following, which can be broken down into the two broad categories of (1) treatment, and (2) monitoring:
(1) TREATMENT - IVIG (intravenous immunoglobulin) (according to guidelines, the treatment has lasted for 5 days, at the dosage of 400 mg/kg/day);
(2) MONITORING - since nerves are distributed throughout the body, there is a chance that the patient might develop respiratory failure and hypotension (where the smooth muscular walls of the vessels can't work properly anymore). Pulse oximetry, blood pressure monitoring and spirometry are recommended for checking respiratory and circulatory functions. We also ask for any swallowing difficulties and pain. Monitoring is usually done every 1-3 hours so that we can know more about the progression and natural course of the disease in the patient.
Since the patient does not walk very well, we are worried that she might develop deep vein thrombosis (meaning that a lesion originating from clotted blood is lodged right in the deep veins of, often but not exclusively, the lower limbs). We thus gave her apixaban (a type of DOAC) as prophylaxis (pre-emptive medication to prevent the condition from occurrence).
Emma is very lucky. After five days of treatment, her condition has dramatically improved and can go to the toilet on her own, with the help of the nursing staff. However, some patients may experience permanent damage leading to the prolonged need for catheterisation. She is referred to a physiotherapist to make sure she can return to her normal life.
[3]
I personally think it's a very interesting case since it traverses traditional boundaries between neurology and urology. It is important for us to investigate along both lines and expand the list of differential diagnoses initially. We also have to be more alert to the patient's infectious, autoimmune and family history, where the patient might respond in a more dynamic way to infections than the normal population. This leads to the emergence of post-infectious autoimmune diseases.
*As usual, all patient names and other identifiable particulars are fabricated for the purposes of patient privacy. This case report is written on the basis that no consent can be practically obtained since the patient has been transferred to the surgical ward shortly after the consultation. Therefore, the focus will be on medical history and symptomatology, as well as the disease in general. All diagrams and illustrations are obtained from the internet (with sources indicated), rather than from the patient.
**For any of you who's interested, that patient had a rocky life - diabetic, hypertensive and immunodeficient, she also had a condition called hyperparathyroidism where those tiny little structures pertinent to the thyroid gland, so known as 'parathyroid glands', got hyperactive. Therefore, there was too much calcium in her blood. The persistent high levels of calcium were responsible for the recurrent kidney stones which led to the recurrent urinary tract infections. It reminds us that one issue can lead to the next. Everything in the body is connected and nothing can be considered in pure isolation.
References and Further Reading:
[1] Sakakibara R, Hattori T, Kuwabara S, Yamanishi T & Yasuda K. (1997). Micturitional disturbance in patients with Guillain-Barré syndrome. Journal of Neurology, Neurosurgery & Psychiatry, 63(5), 649-653.
[2] Khan F, Louisa NG. (2011). Guillain–Barré Syndrome. In: Kreutzer JS, DeLuca J, Caplan B. (eds) Encyclopedia of Clinical Neuropsychology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-79948-3_554.
[3] Willison H, Jacobs B, & van Doorn P. (2016). Guillain-Barré syndrome. The Lancet, 388(10045), 717-727. https://doi.org/10.1016/s0140-6736(16)00339-1.
[4] Usatine RP, Riojas M. (2010). Diagnosis and Management of Contact Dermatitis. American Family Physician, 82(3), 249-255.
[5] Serlin DC, Heidelbaugh JJ, Stoffel JT. (2018). Urinary Retention in Adults: Evaluation and Initial Management. American Family Physician, 98(8):496-503.
[6] Gao X, Fang Z, Lu C, Shen R, Dong H, Sun Y. (2020). Management of staghorn stones in special situations. Asian Journal of Urology, 7(2):130-138. doi:10.1016/j.ajur.2019.12.014.
[7] Khatib HE, Naous A, Ghanem S, Dbaibo G, Rajab M. (2017). Case report: Guillain-Barre syndrome with pneumococcus - A new association in pediatrics. IDCases, 11, 36–38. https://doi.org/10.1016/j.idcr.2017.11.009.
[8] Mallik A, Weir AI. (2005). Nerve conduction studies: essentials and pitfalls in practice. Journal of Neurology, Neurosurgery & Psychiatry 76:ii23-ii31.
[9] Sandler PM, Avillo C, Kaplan SA. (1998). Detrusor Areflexia in a Patient with Myasthenia Gravis. International Journal of Urology 5, 188-190.
[10] Previnaire JG. (2018). The importance of the bulbocavernosus reflex. Spinal cord series and cases, 4, 2. https://doi.org/10.1038/s41394-017-0012-0.