Answer To January's Case

Dear Bloggers

Thank you for waiting for the answer to January's case. I was informed that it might have been a bit too difficult. However, residents still need to be able to understand all the problems in any patient case in order to construct a logical plan of further investigations and / or treatment.

Although this patient had many problems, it is not a rare occurrence for patients of advanced age to accrue disease which muddies the water when trying to make a diagnosis for a main problem; hence Ockham vs Hickham (see below). This is where clinical acumen, logical testing and using the mental probability assessment of common things being common and uncommon things being uncommon comes into play.

At the end of the day, it is sometimes necessary to obtain a biopsy to get the diagnosis - as Prof Lawrence Tierney says "Tissue is the issue". Let's see whether that was necessary in this case.

Professor Masami Matsumura who is well known to this blog for his excellence in problem solving has again astounded me with his opinion on this very difficult case.

We have to consider the contrast between Occam’s Razor and Hickham’s Dictum because this patient is a high aged woman. Did she have SINGLE disease or MULTIPLE diseases? She had multiple processes as follows;
1. Chronic inflammatory condition including neoplastic disease
2. Neuropathy
3. Masses in mouth and submucosa in upper GI tract
4. Heart failure
5. Emphysema

It is impossible to interpret ALL problems within SINGLE disorder. Firstly, I would focus on the chronic inflammatory condition and neuropathy.

Questions 1) Please make a full list of ALL the patient's problems and make assessments according to diagnostic grouping.

I listed problems as follows;
#1 Fever
#2 Weight Loss
#3 Sweats (suspect dehydration)
#4 Fatigue
#5 Normocytic anemia
#6 High ESR
#7 Foot numbness (L4, 5, and S1)
#8 Leg Pain (disappeared)
#9 Unusual scalp feeling
#10 Shoulder Pain (for several years)
#11 Fixed 'shotty' nodes in the groins
#12 Mass in oral cavity
#13 Submucosal mass in upper GI tract
#14 Dyspnea
#15 Tachypnea
#16 Hypoxia
#17 Tachycardia, Atrial Fibrillation
#18 Effusions
#19 Wet early crackles
#20 Cardiomegaly
#21 Pitting edema > 40 seconds
#22 Hypertension
#23 Quinke's sign
#24 ex-smoker
#25 Hyper-expanded chest
#26 Fibrotic change in the lung
#27 Elevated ALP
#28 Impaired Glucose Tolerance
#29 Insomnia
#30 Cataracts *I can’t interpret following finding correctly; Trachea .. with two-fingers appliable to the suprasternal notch I guess this finding was caused by emphysema. (correct - tracheal tug)

ASSESSMENT:
Chronic inflammatory condition including infection, neoplastic, or autoimmune disease should be considered from #1 Fever, #2 Weight Loss, #3 Sweats, #4 Fatigue, #5 Normocytic anemia, and #6 High ESR. This patient disclosed B symptom. Vasculitides, lymphoma, tuberculosis (TB), or infective endocarditis (IE) is suspected.
Interpretation of #7 Foot numbness is peripheral neuropathy. In this case, mononeuritis multiplex or polyneuropathy should be considered. Most likely etiology is vasculitides, especially polyarteritis nodosa. Microscopic polyangiitis is one of candidate. However, kidney function was normal and normal urinalysis except trace of protein was observed.
Vasculitides including polyarteritis nodosa is suspected from #8 Leg Pain. Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are suspected from #9 Unusual scalp feeling and #10 Shoulder Pain.
Lymphoma or another malignant tumor has to be ruled out because she disclosed #11 Fixed 'shotty' nodes in the groins, #12 Mass in oral cavity, and #13 Submucosal mass in upper GI tract.

Multiple myeloma is not candidate in this case. I would introduce one pearl of Dr. Tierney. “The three no’s of myeloma: no FEVER, no splenomegaly, no elevated ALP”

Heart failure is apparent because of #14 Dyspnea, #15 Tachypnea, #16 Hypoxia, #17 Tachycardia, Af, #18 Effusions, #19 Wet early crackles, #20 Cardiomegaly, and #21 Pitting edema >40 seconds. Her pulse character was consistent with atrial fibrillation (Af). WET EARLY CRACKLES at the base means early sign of heart failure. Pitting edema >40 seconds was derived from heart failure too. If patient's serum albumin is low, pit recovery time will be within 40 seconds with one exception if there is long standing pitting edema caused by low serum albumin. Long history of edema will cause tissue fibrosis.

Quinke's sign doesn’t mean high specificity of aortic regurgitation (Ar). However, aortic regurgitation due to hypertension is suspected. Of course IE must be ruled out. Interpretation of #24 Ex-smoker, #25 Hyper-expanded chest, and #26 Fibrotic change in the lung are emphysema.

My differential diagnoses are as follows:
Vascular: Less likely Infection: IE, TB (TB is always differentiated in feverish patient in Japan) Neoplastic: Lymphoma, Paraneoplastic syndrome
Autoimmune: Polyarteritis nodosa, Microscopic polyangiitis, PMR/GCA, Still’s disease, SLE, Wegener’s glanulomatosis, Sarcoidosis, Churg-Strauss syndrome
Toxic: Less likely
Metabolic: Diabetes Trauma/Degenerative: Less likely
Iatrogenic: Less likely Idiopathic: Less likely
Congenital: Less likely plus she had Af, HTN, Ar, heart failure, and emphysema.

2) What other laboratory study or studies would you consider performing in this patient?

I would order the following tests; LDH, blood glucose, HbA1C, ferritin, P-ANCA, C-ANCA, and ANA Three sets of blood cultures Cardiac echo to confirm vegetation and kinetics of heart muscle Sputum acid fast stain and cultures for TB Angiogram of celiac, mesenteric, and renal arteries Biopsy of sural nerve and mass in mouth if possible Submucosal mass in upper GI tract should be carefully monitored ALP should be monitored

3) What is your top suspected diagnosis for the MAIN problem in this patient and how would you establish the definitive diagnosis?

In Japan, microscopic polyangiitis is not so rare. Polyarteritis nodosa and Wegener’s glanulomatosis are rare in Japan. But I highly suspect polyarteritis nodosa in this case. I refer one of criteria of Polyarteritis Nodosa. She might have three criteria (bold & italics: 1, 4, and 5). 1990 Criteria For the Classification of Polyarteritis Nodosa

1. Weight loss; 4 kg Loss of 4 kg or more of body weight since illness began, not due to dieting or other factors

2. Livedo reticularis Mottled reticular pattern over the skin or portions of the extremities or torso

3. Testicular pain or tenderness Pain or tenderness of the testicles, not due to infection, trauma, or other causes

4. Myalgias, weakness or leg tenderness Diffuse myalgias (excluding shoulder and hip girdle) or weakness of muscles or tenderness of leg muscles

5. Mononeuropathy or polyneuropathy Development of mononeuropathy, multiple mononeuropathys, or polyneuropathy

6. Diastolic BP >90 mm Hg Development of hypertension with diastolic BP higher than 90 mm Hg

7. Elevated BUN or creatinine Elevation of BUN >40 mg/dl or creatinine >1.5 mg/dl, not due to dehydration or obstruction

8. Hepatitis B virus Presenece of hepatitis B surface antigen or antibody in serum

9. Arteriographic abnormality Arteriogram showing aneurysms or occlusions of the visceral arteries, not due to arteriosclerosis, fibromuscular dysplasia, or other noninflammatory causes

10. Biopsy of small or medium-sized artery containing PMN Histologic changes showing the presence of granulocytes or granulocytes and mononuclear leukocytes in the artery wall

For classification purposes, a patient shall be said to have polyarteritis nodosa if at least 3 of these 10 criteria are present. The presence of any 3 or more criteria yields a sensitivity of 82.2% and a specificicy of 86.6%. BP = blood pressure; BUN = blood urea nitrogen; PMN = polymorphonuclear neutrophils. Lightfoot RW Jr, Michel BA, Bloch DA, Hunder GG, Zvaifler NJ, McShane DJ, et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum 1990;33:1088---93.

PMR/GCA is suspected too. However, these diseases don’t disclose neuropathy. Churg-Strauss syndrome is not likely because she didn’t have history of asthma. SLE and Still’s disease are not highly likely.

Lymphoma is possible. IE and TB have to be ruled out.

Angiogram of celiac, mesenteric, and renal arteries and/or biopsy of sural nerve are needed to establish the diagnosis. I hope my hypothesis is correct. If it is correct, management of disease will be tough. Her cardiac and lung functions are not good. Opportunistic infection should be CAREFULLY monitored.

Professor Gerald Stein has also provided another excellent assessment below:

1. Problem List
# Fever
# Sweats
# Fatigue
# Weight Loss
# Numbness of her feet
# Dyspnoea
# Initial headache
# Leg Pain
# Shoulder Pain
# HT
# DM
# lymphadenopathy
# tachycardia(?AF)
# Quinke's sign(AR)
# ^JVP
# leg edema
# tachypnea
# dullness lung bases
# bibasilar crackles
# decreased light touch feet
# anemia
# ^ALP
# ^ESR large
# 2x3 cm mass arising from the hard palate
# chest xp bilat effusions ^ heart shadow
# EGD submucosal mass

1. Assessment 1.Temporal arteritis/GCA evolving from PMR, ? associated with CA S/O CA[gastric lesions CA, MALT]
2. Heart failure, ? IHD, D, AR[?HT related, R/O Lues]
3. DM sensory neuropathy
4. HT
5. Anemia, ? to GCA, R/O GI bleed
6. Gastric Mass, R/O CA, etc
7. Palate mass, R/O CA

2. Anemia studies-Fe, smear, ferritin, etc Biopsies as above+ Temporal Artery Bx, BS, HAIc, ECG, cardiac ECHO, Lues tests,

3. see assessment> Temporal Artery Bx Response to Prednisone 40 mg/d; Aspirin for AF with PPI; Tb eval before Prednisone

Professor Gurpreet Dhaliwal, University of San Francisco has kindly joined this month's opinion on the case. He has also raised some very important and interesting points. Thanks!

I have departed from the suggested format in order to share my general impressions and leading diagnoses:
This 80 year old woman has a subacute inflammatory illness of unknown etiology. Her age increases susceptibility to cancer and infection over other classes of disease (e.g., rheumatologic) and her lifelong smoking substantially increases her probability of cancer

Peripheral neuropathy (with an unusual migratory component) is described. Given her age, I wonder more about paraneoplastic neuropathy than autoimmune conditions, although intermittent arterial ischemia of the limb or the nerves of the limb caused by vasculitis, could mimic these symptoms. The transient leg pain (among other things) makes me wonder about this. Infections are infrequently implicated in peripheral neuropathy.

Generalized lymphadenopathy has a large differential diagnosis including infection (mycobacterial, fungal, viral), malignancy (lymphoma, metastatic carcinoma), and autoimmunity (sarcoid, lupus).

A hard palate mass could be a clue to a disease with a predilection for the hard palate (e.g., Wegeners, Behcets), but as described, it sounds like a torus palatinus

Many features point to new CHF (history of hypertension, new atrial fibrillation, dyspnea, hypoxia, crackles, effusions). I note that the JVP was normal, but this can be a challenging physical exam finding for even experienced practioners. Quinke’s sign is typically associated with chronic AI, but I suspect the specificity is not 100%. The murmur of AI was not detected, it is often quite soft and relies on proper patient positioning.

Her marked normocytic anemia is most likely anemia of chronic inflammatory disease. Bone marrow involvement must be considered with an elevated alkaline phosphatase and normal GGT (suggesting a bone source of alkaline phosphatase), but the other cell lines are not involved. If the alkaline phosphatase elevation was of the liver variety (with no other abnormal liver function tests), then an infiltrative disease of the liver, such as lymphoma or tuberculosis, would merit even stronger consideration.

Finally, there is a mention of a submucosal mass of OGD (EGD), but the location is not noted. Certainly a lymphoma or carcinoma may cause this, perhaps more likely than any infection (e.g., TB) or rheumatologic condition.

The ESR of > 100 must be noted, but it lacks specificity other than confirming the general impression of inflammation -- of unknown etiology in this case.

Here are my hypotheses:



INFECTION: In general, I do not suspect infection here. Other than her age, there is no reason to suspect a chronic indolent infection such as mycobacteria or fungus. Endocarditis would be a very reasonable explanation, although she failed to improve on broad spectrum antibiotics, so SBE seems less unlikely.



AUTOIMMUNITY: The unusual scalp sensation, marked anemia, and ESR > 100 are consistent with giant cell arteritis (temporal arteritis / polymyalgia rheumatica / takayasu’s). GCA is frequent cause of FUO in the elderly and is increasingly recognized as affecting the aorta (e.g., majority of patients with biopsy proven TA have aortic involvement on PET scan.) If so, perhaps this would explain both a sign of aortic insufficiency and limb ischemia. This would be determined by temporal artery biopsy. The lymphadenopathy and oesophageal/gastric mass would be unusual. The features of other vasculitides



MALIGNANCY: The submucosal EGD mass, lymphadenopathy, age, and smoking history make cancers a primary concern. This could represent disseminated lung cancer (hiding in the reported fibrotic area), gastric cancer (based on the EGD mass), or lymphoma. I am most concerned about malignancy, although it is not clear why she has developed atrial fibrillation / heart failure at the same time.

I would pursue the following tests:
Echo to assess for CHF and aortic valve integrity
Biopsy and culture of neck lymph node and EGD mass
If all of the above are unrevealing, I would consider temporal artery biopsy.

The above assessments were very similar to my own and in view of the extensive detail therein, I feel that I cannot surpass them. Hence, I will not go into raptures of my own assessment this month but simply explain what happened next :-)

As Prof Matsumura mentioned above, microscopic polyangiitis (MPA) is not so rare in Japan whereas PAN and Wegener's granulomatosis are rare. However, the MPO-ANCA was found to be slightly positive and hepatitis B & C viruses were negative thereby, in my own opinion, elevating the diagnosis for MPA despite the absence of renal impairment.

However, in MPA renal dysfunction is almost universal when there is the onset of vasculitis. These findings are dichotymous. Hence, the only way to get the diagnosis was to get tissue (that being the issue!) and ruling out infection from Tb and infective endocarditis and excluding malignancy such as a disseminated GI cancer and lymphoma.

In the end, the patient underwent biopsy of the sural nerve which showed a leukocytoclastic vasculitis. There were no granulomata present.

The histopathology final report was consistent with Polyarteritis Nodosum rather than microscopic polyangiitis.

This is in keeping with the opinion of Professor Matsumura but somewhat surprising in view of the elevated MPO-ANCA level.

Tests for endocarditis and tuberculosis were negative.

Repeat gastroscopy revealed ulceration with no malignancy present.

The lesion identified in the hard palate was indeed Torus Palatinus ; a benign lesion of no signficance.

The patient had confirmed heart failure and and aortic regurgitation was confirmed by cardiac echo. This was effectively controlled with standard therapy.

Steroid treatment was commenced (with PPI cover) and there was resolution of most symptoms. Particularly striking was the improvement in malaise, appetite and energy levels (all steroid effects). The patient started walking from being bed bound just a few days earlier and continues to improve on 40mg Prednisolone /day.

For the manifestations, investigations and treatment of PAN, please see UpToDate 16.3

I would like to take this opportunity to thank all of the doctors who took part in January's case responses. The case answer has been posted late for several reasons, but mainly that I have been too busy ! :-o

Stay tuned for more discussions and cases in the future!

Please accept my apologies for the errors in spacing in this article. This seems to be due to a recent error in the Blogger programme.

A Word Of Caution in Overdose

Dear Bloggers

Today I want to touch on the topic of drug overdose.

This is a common medical problem. Overdoses should always be taken seriously and investigated and treated vigorously in order to avoid morbidity and mortality.

Although the textbooks tell us about individual drug overdoses, the predicted symptoms, signs, investigations and treatments, they do little to tell us how to manage mixed overdoses. The reason is, patients can take several drugs in combination at various different doses and with drugs that have different rates of release, absorption, volume of distribution and elimination kinetics. This is a total minefield for the physician.

In terms of working out what you are dealing with and what to do, always use a toxicology reference or database. A very good one in the UK is called ToxBase, although Skyscape.com also has several toxicology titles available for PDAs which give standard and sound advice. Checking UpToDate is also advantageous in such circumstances and of course the standard textbooks.

Charcoal

Although charcoal therapy is commonly advised to be given if the overdose is within an hour of ingestion, it does not mean that charcoal should not be given if the OD it past one hour. Quite the contrary. As some drugs are in a slow-release formulation, it may take several hours for the full drug dose to be released and absorbed, thereby resulting in toxicity and delayed elimination. Hence, even if the OD is known to be past one hour or the time of ingestion is unknown, charcoal should still be given EXCEPT if there is evidence of bowel perforation or obstruction. Impaired consciousness is a contraindication to charcoal ONLY UNTIL the patient has had their airway secured with an endotracheal tube. Multiple doses of charcoal might need to be given rather than just the customary one dose.

Serum and Urine Drug Screening

Patients should be checked for several compounds either by serum or urine examination including NSAIDs, acetaminophen (paracetamol [UK]), benzodiazepines, lithium, neuroleptics, tricyclics, amphetamines, canabinoids, opiates/opioids, ethylene glycol, methanol, ethanol etc..

ABG

Arterial blood gas should also be taken to assess for acidosis or alkalosis - these may be clues indicating the type of overdose. A metabolic acidosis with a raised anion gap might suggest alcohol, methanol, ethylene glycol in the context of an overdose. A respiratory alkalosis might suggest early NSAID overdose which may later change to a metabolic acidosis.

Anion Gap and Osmolar Gap

Check the Anion Gap [Na -(Cl + HCO3)]; >16 is + but truly significant is >25.

Causes of Raised Anion Gap Acidosis remember KUSSMAL.

K etoacidosis
U remia
S alicylates
S epsis
M ethanol / ethylene glycol
A lcohol
L actic acidosis

Osmolar Gap = Measured Osmolality - Calculated Osmolality;
Calculated Osm = 2 x Na + Urea + Glucose

Normal mosm/kg. It is raised in poisoning from methanol, ethylene glycol etc.

ECG

Check an ECG -- look for the evidence of acquired Long QT. Patients are at risk of Torsade de Pointes if the QT is significantly prolonged and such patients need to be in an ICU monitored bed. Remember in such cases, magnesium, defibrillation and atrial/ventricular overdrive pacing are the treatment of choice for drug induced Torsade and NOT other antiarrhythmic agents that can make the situation worse!

Radiology

Check an Xray of the chest -- look for potential aspiration and pulmonary oedema. Sometimes tablets are aspirated and cause lung collapse and chemical damage. The CXR or a chest CT may show the tablet(s) and of course, emergency bronchoscopy for removal!

Abdominal Xray can be performed which may reveal radio-opaque drugs such as heavy metals, iodinated compounds, lithium, enteric coated tablets and NSAIDs etc..

CT head scanning should be performed in the unconscious patient to exclude cerebral oedema or another cause for the unconsciousness e.g. sub-dural haemorrhage.

Infection Screening

In those circumstances when the patient has a fever, unconsciousness and features of infection, a lumbar puncture should be performed to rule out meningitis (after CT head indicates no raised intracranial pressure).

Check blood, urine and sputum cultures as well.

Aide mèmoire and trial of treatment

In the unconscious patient, make sure to check pupillary size. Small 'pin-point' pupils and a low respiratory rate can signify opiate overdose. Be sure to proceed with a trial of naloxone to see if it rouses the unconscious patient. Don't wait for the toxicology report as the patient might have already stopped breathing. Naloxone is safe and it is rewarding to see a completely unconscious patient wake within seconds of the antidote only to complain to you 'Why did you wake me up!', and not thank you for saving their life :-(

Conversely, dilated pupils might signify an SSRI, Cocaine, Amphetamine OD etc...

50 of 50

Moreover, remember that NSAIDs, insulin and oral diabetes agents, to mention just a few, in overdose can commonly result in hypoglycaemia. Serum and CSF glucose concentrations DO NOT correlate well so remember to give the 50ml of 50% dextrose even if the capillary bedside glucose appears normal.

Acetaminophen OD and its treatment

Some hospitals are not able to do rapid acetaminophen levels -- they may take a week to come back from the reference lab! Hence, in those institutions, when it is not known what the patient has ingested and it is not possible to test for the drug or that it takes longer to get the result than would be clinically useful, the antidote to acetaminophen should be administered which can be oral methionine or N-acetylcystine (i.v.).

In view that it might take 48 hours for a significant acetaminophen OD to become clinically detectable with hepatic necrosis and fulminant liver failure, as physicians, we cannot take chances by ruling out that the patient has not taken an acetaminophen OD even if it is considered to be an uncommon occurrence. Remember, any prescribed drug or over the counter drug is a potential poison in overdose. However, the drugs commonly ingested in OD and which can be fatal, should be investigated and treated. If unable to be rapidly tested for, then consider to treat anyway! Remember that liver and renal function tests plus, particularly ABG and INR testing are important clinically and prognostically in liver failure from acetaminophen overdose. Prolongation of the INR, hypoglycaemia, renal failure and acidaemia portend a poor prognosis (King's Criteria).

Don't take risks. Don't take chances. Investigate and treat accordingly.

Further Care

Remember that when the patient gets better you should keep them under close supervision to avoid repeated intentional harm within the hospital. High risk patients are especially vulnerable. This means 24 hour supervision and no less.

Psychiatrists

Psychiatric input is necessary as soon as they are over the acute phase of the attempted suicide. DO NOT JUST SEND THEM HOME. Psychiatric assessment and / or further treatment may be necessary. Not all suicidal patients need to be admitted for psychiatric assessment. This can be done as an outpatient if the patient is deemed low risk for further suicide attempts.

For a fuller explanations on the various drug overdoses please see the references mentioned above or any major text on the subject.

Please consider :-)

January's Case

Dear Bloggers

Here is an anonymised case for January. Please have a go! Drop me your opinions on the case and we can see if your are right!

This 80 year old female presented with a two month history of the following symptoms:

• Fever
• Sweats
• Fatigue
• Weight Loss
• Numbness of her feet
• Dyspnoea
  

The symptoms started abruptly two months before with onset of fever. The patient took her own temperature which was about 38 degrees Celsius. She was unable to say if there was day-night variation in the fever. There were no associated chills or rigors.

The patient noticed sweating, albeit intermittently, and only when she had the fever. She denied drenching night sweats.

The fatigue was apparent from the outset and continued throughout the two months prior to and during the admission to hospital. There was associated weight loss noticed by the patient with her clothes feeling larger on her and her wedding ring becoming loose.

The numbness occurred initially in both her hands and feet and became constant in the latter and disappeared in the former after several weeks. On admission, she complained of only foot numbness up to the ankle area.

The patient also noticed worsening dyspnoea especially on exertion. She denied orthopnea, cough, sputum, wheeze, haemoptysis.

On further questioning she admitted to further symptoms of

• Initial headache: this headache occurred at the beginning of the symptom complex. She was unable to denote the severity on the pain scale. There was no throbbing nature to the pain but she did admit to an unusual feeling on her scalp. There was no visual disturbance, no jaw or tongue claudication.
• Leg Pain: she admitted to initial upper leg pain which soon disappeared. There was no complaint of this on admission. The patient did not complain of weakness.
• Shoulder Pain: this was apparently a long standing problem going back several years and had not worsened prior to or during the admission.

The patient had initially been admitted to a local clinic for investigation and treatment. It was suspected that the patient had an "infection" and she was commenced on piperacillin and sulbactam without improvement of symptoms or resolution of the fever. She was referred to another hospital for further investigation.

Previous Medical History

• Hypertension
• Impaired Glucose Tolerance
• Insomnia
  

Medication

• Rampiril 10mg/day
• Diazepam 5mg once nocte

Family History

Nothing relevant

Social History & Habits

She lived with her family. Her husband was deceased. She was an ex-smoker although only recently having given up.
She did not consume alcohol and had never received a blood transfusion, tattoos or needle stick injury.

She had no pets and had never travelled abroad.

Review of Body Systems (questions to patient only; no physical exam at this stage)

CVS: No palpitations, chest pain, leg pain on walking
RESP: as above. No sinus pain, no epistaxis,
ABDO: No abdominal pain or swelling. No nausea, vomiting, diarrhoea, constipation, malena, haematochezia or jaundice.
MUSC-SKEL: No muscle or bone pain. No joint swelling or morning stiffness.
URO-GEN: No urinary symptoms or vaginal discharge. No post-menopausal bleeding. No change in the colour of her urine.
CNS-PNS: No visual disturbance, no hearing disturbance, no speech disturbance. No weakness or other new sensory disturbances. No seizures in the past.
ENDO: No polyuria, polydipsia. No alteration in hot or cold tolerance. No history of renal stones.
SKIN: No complaints.

On Examination

General: She appeared chronically unwell. She was alert, conversant although unclear with precise history. She appeared sweaty. Conjunctivae appeared pale. No cyanosis.

Lymph Nodes: Non-tender lymphadenopathy was present at both jugulodigastric nodes and small, fixed 'shotty' nodes in the groins.

Mouth: large, 2x3 cm mass arising from the hard palate. Pink colour, smooth, no ulceration or bleeding. Patient denied trauma to the identified area.

CVS: Pulse 140 per minute, irregulary irregular with low volume quality. It was not possible to ascertain collapse or slow rising nature. BP 120/70mmHg in the right arm in the supine position. Sitting BP was not performed. JVP was 5cm and with an irregular peak in keeping with the irregular pulse. Quinke's sign was positive.
Heart sounds 1 & 2 were present with no obvious 3rd or 4th sound. No murmur evident. There were no carotid bruits.
Legs revealed pitting oedema >40 seconds in the posterior ankle region. There was no clinical evidence of DVT.

RESP: Resp Rate 26 per minute and regular. SpO2 93% on ambient room air. Trachea central with two-fingers appliable to the suprasternal notch. The chest was mildly hyper-expanded, dull to percussion bilaterally at the bases with 'wet' early crackles.

ABDO: Soft, flat, non-tender. No hepatosplenomegaly, no ascites. Bowel sounds normal. Renal angles revealed no tenderness. Rectal exam - no masses and blood was absent.

MUSC-SKEL: No joint pain or swelling on passive movement in any of the large or small joints. Muscles revealed no tenderness.

PNS:
Tone: Normal throughout in upper and lower limbs.
Power: Normal 5/5 throughout
Reflexes: Normal throughout in upper and lower limbs.
Coordination: Within normal limits
Sensation: Indeterminate change in hands for light touch; loss of light touch in soles and dorsum of both feet. Temperature, nociception, vibration not measured.
Babinski: negative bilaterally (flexor plantar)

CNS:
II: bilateral cataracts, normal constriction to light and accommodation. Visual fields difficult to accurately determine but grossly within normal limits for age.
III / IV / VI: Within normal limits
V: Motor and Sensory within normal limits
VII / VIII / IX / X / XI / XII: Within normal limits

No cerebellar signs.

Lab Studies

Hb 8.6, WBC 6.6, MCV 92, Plts 24.6 (normal). AST / ALT / gamma-GT / Bilirubin within normal limits. ALP 432 (ALP 1 iso-enzyme elevated). BUN and Creatinine within normal limits. Creatinine Kinase (CK) within normal limits.

Serum electrophoresis normal. Bence Jones protein not tested.

Coagulation normal. Urinalysis normal except for trace of protein.

ESR >100mm/hr.

HBV and HCV negative.

Chest Xray: Bilateral small effusions. Hyper-expansion. Cardiac silhouette slightly enlarged. No mass lesions or bone erosions.

CT of Chest and Abdomen: Bilateral effusions. A small area of fibrotic change in the right anterior lung. Normal amount of pericardial fluid. No mass lesion identified. Liver normal looking. Spleen normal size. Kidneys - normal texture, no hydronephrosis. Pancreas appeared normal.

Oesophagogastroduodenoscopy (OGD): revealed a submucosal mass; no biopsy had been taken on initial inspection.

Questions

1) Please make a full list of ALL the patient's problems and make assessments according to diagnostic grouping.

2) What other laboratory study or studies would you consider performing in this patient?

3) What is your top suspected diagnosis for the MAIN problem in this patient and how would you establish the definitive diagnosis?

The answer to this case will be available in the near future. Please send in your responses and get published online. Anonymous replies are welcome too!

Ever Heard of Evernote?

Dear Bloggers

Today, I thought I would introduce you to something truly unique and ultra-portable!

It is the new internet and phone based application called Evernote.

This application is superb for keeping notes wherever you are. You can type your notes on your PC/Mac, iPhone or PocketPC (Windows Mobile) which then automatically get uploaded to your account in the web-cloud. These notes can then be viewed or edited on any of the above communication platforms.

What actually sets this application far apart from the others e.g. Google notes or MobileMe, is that the application is able to search your entire documents for words, and that includes words within pictures!!! Say for example, you have written information within a picture, Evernote will find it! Even photographs can be searched for words. Great!

You can also upload voice notes as an additional feature.

This is great for physicians who want to look up some information from their notes on the go or take a quick note in a lecture or just to upload their thoughts on conditions or for reminders.

Having tried this application, I can highly recommend it. It is easy to use, has the same features across various platforms, is quick to find information and immediately backs up information. Perfect!

The application is FREE! Yes, FREE! Upload information per month is 40 megabytes but for those with more gelt, $45 per year gets you a monthly 500 megabyte upload quantity. You decide.

If you are interested in checking this out, click on the following link.

A Different Way To Perform Male Urinary Catheterisation

Dear Bloggers

Welcome to 2009 !!

Today I would like to discuss about, what I regard as the most appropriate technique for male urinary catheterisation.

Catheterisation of the male bladder is in my opinion a difficult technique to get right. Why you may ask [with a smirk and a frown]? Because it is not taken seriously enough by medical personnel. The disregard of proper aseptic technique can lead to hospital acquired infections with its attendant morbidity and potential mortality. If it were a central venous line insertion, the patient would have their skin sterilised with alcohol / iodine and draped before entering the vascular space. With the bladder however, there seems to be a more relaxed, less serious approach to the appropriate use of aseptic technique. This is clearly not ideal and needs attention.

I have seen one worrisome technique which involves using long sterile forceps to introduce the catheter into the urethra without using full aseptic procedures. This has the inherent risk of introducing infection and is prone to technical failure.

I would therefore like to introduce you to a different technique which uses full aseptic technique and is easier to perform and is used as the norm in the UK system.

Step 1: Explain to the patient what you are going to do. You should never start any technique without obtaining informed consent from the patient. Do not take it for granted that the patient will say yes to any procedure. In an unconscious patient, catheterisation should be considered in the context of it being in their best interest for purposes of monitoring urine output and relieving retention.

Step 2: In a private examination area, fully expose the penis. NOW WASH YOUR HANDS USING STERILISING DETERGENT. Set up a sterile procedure pack on your bedside trolley. On the sterile procedure area, ensure you have a kidney-dish, a fluid receptacle, cotton wool, sterile gel, one or two 10ml syringes, saline and / or antiseptic fluid, an appropriately sized male urinary catheter and sterile gloves of appropriate size. A 10 or 12 French size Foley catheter is usually appropriate for most males. Put on the sterile gloves and then drape the inguinal area with a sterile paper sheet with a hole made in the centre to allow the penis to be placed through it. Some kits come with the hole already made.

Ensure a catheter bag is prepared in advance for collecting the urine.

Step 3: Prepare sterile saline or antiseptic liquid in the small container on your sterile procedure pack. Open the tip of the catheter pack with only the tip of the catheter allowed to protrude and replace it on the sterile tray. Open a new sterile gel used only for catheterisation. Do not use one previously opened as there is a risk of contamination.

UK hospitals have sealed Lignocaine gel specially prepared for catheterisation. This type of gel reduces the pain associated with the procedure. Load 10ml of sterile water or saline into a disposable 10ml syringe for eventual injection into the balloon port of the catheter.

Step 4: With your non-dominant hand, in this example the left hand, retract the foreskin of the patient (this is now a dirty hand and should never be used to handle aseptic utensils after this). With the clean dominant (right) hand pick up a cotton wool ball soaked in saline/disinfectant and wipe the tip of the penis to remove any debris. Repeat this with a clean cotton wall ball. Remember to throw your dirty disposables in a bin and never put them back on your sterile tray! Some doctors double glove the clean hand in advance and remove the top glove to ensure the remaining glove is definitely sterile.

Step 5: Now pull the penis vertically until straight and squeeze the gel down the external os into the urethra via the syringe. Aim to instill approximately 10ml of gel. Gently squeeze the outer corona of the penis to close the external os for about 2 minutes to stop the gel coming out and to give time for the lignocaine to anaesthetise the urethra. If the plain gel comes in a tube, use the additional 10ml syringe and pre-load it with the gel before instilling it down the male urethra.

Step 6: Now the tricky bit. Pick up the opened catheter with your aseptic dominant (right) hand and place the tip into the external os of the penis and release the external pressure on the corona whilst still holding the penis straight and vertical. Extend the catheter slowly down the urethra by pushing forwards and withdrawing the catheter from its protective sheath.

The catheter may need to be moved backwards and forwards as the gel does not always coat the entire urethra.

When the prostate is reached there will be some resistance. Push slightly more on the catheter until the resistance is overcome. Sometimes the catheter needs to be twisted in a corkscrew motion to achieve entry past the prostate.

NEVER FORCE THE CATHETER as it can create a false track inside the prostate. If in trouble call your senior doctor or the on-call urologist for assistance as soon as possible.

Sometimes using a larger French size catheter can achieve entry where smaller diameter catheters have failed.

Another technique is to use a stiffer catheter made from silicon and plastic polymer to achieve entry.

Step 7: Advance the catheter to its full length and place the open end in the disposable kidney-shaped dish to collect any escaping urine. Inject 10ml slowly into the balloon port. If the patient experiences pain then STOP as the tip of he catheter may still be in the distal urethra. Advance the catheter further forwards and then retry.

All being well, the balloon should inflate without resistance. Now pull the catheter gently until you feel mild resistance (the balloon should be at the neck of the bladder). The urine should now be flowing out of the catheter's open end and attach it to the prepared catheter bag.

Step 8: Remember to retract the foreskin to avoid acute paraphimosis. Wipe up any excess gel and remove the drapes and re-gown the patient's lower region.

Step 9: Remember to measure the residual volume of urine, which will then allow you to ascertain the initial output in one hour. [After 1 hour, output equals total volume minus the residual volume; this needs to be followed hourly if clinically desirable]. Aim to attach the catheter bag to a dedicated stand or bedside structure so that the lower tip of the bag avoids touching the floor as it is otherwise a risk for contamination and hospital acquired infection. Ensure the bag lies at a level lower than the patient's bladder so that urine can actively drain away.

You're done! Once well practised, this technique should take 5-10 minutes to do (without complication) but has inherent measures in place to try and prevent infection through avoiding unnecessary contamination and uses a sterile gloved hand to do the manoeuvres rather than forceps.

Please consider this as an alternative technique for your patients.

As additional advice, in those patients with haematuria or heavy urine contamination, catheters can become blocked and if this does occur, you will hopefully get a call from the friendly ward nurse informing you that the patient's urine output has dropped or stopped. Please see my last blog about the assessment of reduced urine output. Any patient with a Foley catheter in situ who has a significant drop in urine output and who has no obvious reason for this should have catheter occlusion considered as a potential cause.

One way to tell is to instill 50ml of sterile water down the free end of the catheter and then to suck back on the plunger to see if fluid comes back out. If you get free flow of urine back then the catheter is unblocked. If nothing comes back then a new catheter should be placed instead. If only the water comes back then there may be a problem occurring higher up in the urinary system to account for the lack of draining urine or there may be an intra-renal or pre-renal cause that will need further assessment.

This set of instructions is only but a guide. At all times clinical judgment should be used when performing any invasive technique and the ultimate responsibility is yours. If in doubt, always discuss matters with your senior doctors before performing any invasive technique with which you have suboptimal experience and / or confidence. If you are in doubt, it is better to defer performing the technique yourself to someone who can do it (and preferably they can teach you how to do it at the same time). I do not subscribe to the adage of 'see one, do one, teach one' as it is prone to failure and teaching of poor technique. As a friend once said to me 'it is not practise that makes perfect but it is perfect practise that makes perfect'. Now I do subscribe to that !

Please consider....

The Knee Jerk Response To Urine Output

Dear Bloggers

Today I want to have a final rant for 2008!

The rant is about the sometimes observed 'knee jerk reaction' that one sees by inexperienced physicians when the patient's urine output is low and furosemide is given to 'make the patient pee'.

Low urine output means assessment of the cause rather than just pumping diuretic into the patient which may makes matters far worse.

For example, low urine output might mean the patient has a urinary tract obstruction (post-renal), hypoperfusion from hypovolaemia (pre-renal) or intrinsic renal failure from an insult (e.g. ATN).

When one assesses this problem, take further history from the patient. They may tell you that they have trouble passing urine and / or a painful lower abdomen or distension suggestive of urinary tract outflow obstruction. On the other hand, it may be more clear whereby bleeding may have already been diagnosed e.g. upper GI haemorrhage. The patient might be taking nephrotoxic drugs, have sepsis or a local glomerulonephritis. The causes of pre -, intra-, and post-renal impairment are too many to discuss on this blog.

However, in patients who have low urine output, suffice it to say that the physical examination is of prime importance in addition to looking at the sequential laboratory studies, to identify the cause and follow the progression or improvement respectively.

When one examines the patient, start generally and then focus on the individual systems.

• Does the patient look ill? Confused? Sweaty?
• Then look at the hands! Check for those splinter haemorrhages as endocarditis can cause renal failure. Assess for encephalopathy by checking for flap (asterixis) -renal failure can cause flap the same as for liver failure and CO2 retention.
• Check the pulse - is there a tachycardia?
• Assess the fingers. Are they cold suggestive of vasoconstriction?
• Check the blood pressure - is there hypotension?
• Check the skin turgor on the dorsum of the hand / arm / inner thigh? Think to yourself, could this be dehydration?
• Feel for axillary sweaty - this is lost in dehydration
• Look at the conjunctivae to assess for anaemia - patient could be in a hypovolaemic state from bleeding
  
• Check the tongue & mucosa for dryness - a sign of possible dehydration
• Check the JVP - is it raised ? (could be a sign of CHF) or is there guttering (sign of hypovolaemia).
• Check the respiratory rate and rhythm - Is there Kussmul respiration / Air hunger -- can be seen in metabolic acidosis (renal failure), bleeding etc
• Listen to the chest - is there a focus of infection? Are there effusions / crepitations of heart failure?
• Listen to the heart for murmurs, added sounds
• Inspect the abdomen - is there a focus of infection? Are there signs of liver disease ? (liver failure can result in renal failure - hepatorenal syndrome)
• Are the renal angles tender ? (pyelonephritis / pyonephrosis)
  
• Can you feel a distended bladder in the lower abdomen? It is dull to percussion and when pressed and the patient may say they want to pass urine.
• Are there any abdominal bruits? Might suggest renal artery stenosis or a dissection if there is a compatible history
• Is there pitting oedema of the lower limbs? Might suggest liver disease, nephrotic syndrome, cardiac failure, venous obstruction, lymphatic obstruction or a low protein state.
• Look at the urine in the catheter bag (if one has been placed already) - measure the total amount since it was last checked. Look at the colour - is it dark suggestive of concentrated urine (hypovolaemia) or straw coloured in the euvolaemic state. Is it orange - bilirubin or red - bloody?
• Consider a rectal examination to look for GI bleeding and / or an enlarged prostate gland and / or malignancy.
  

The above features can help you to understand whether the patient is hypovolaemic, euvolaemic or hypervolaemic and a clue of the potential cause.

A patient with a hypovolaemic state (cold hands/feet, tachycardia, decreased skin turgor, hypotension, no axillary sweating, low JVP, dry tongue, dark small volume urine) should be given fluid to replenish the circulation and NOT diuretics! The reason for the decreased urine output is a result of ADH release and upregulation of the renin-angiotensin-aldosterone (RAS) system to retain water to maintain the circulation. Using a diuretic can result in worsening renal failure at the detriment of the patient. Yes, the frusemide splurge may make the doctor and nurses feel better that the patient is passing some more urine but the worst will be yet to come with the incipient renal failure.

A patient with an hypervolaemic state e.g. CHF, can have a low urine output as a result of vasoconstriction because of low cardiac output. Frank Starling forces denote that when the myocardium is overstretched (as in systolic heart failure), the muscles contracts less. Hence, to maintain blood pressure, the peripheral resistance increases which can reduce kidney perfusion and cause reduced urine output. Moreover, such patients also can have a high RAS activity worsening matters. In this situation, blocking angiotensin 2 production or activity (ACE-I / ARB) and aldosterone (with spironolactone) plus off-loading the circulation with a loop diuretic are the mainstay of conservative therapy. In this situation, it can improve the urine output quite appropriately.
A hypervolaemic state is demonstrated by symptoms and / or signs of CHF, liver disease, nephrosis etc. One might see a raised JVP, normal skin turgor, oedema around the eyes (nephrosis usually), pitting oedema of the extremities, abdominal ascites etc.

In a euvolaemic state, none of the adverse features seen in either the hypovolaemic or hypervolaemic states should be seen. One should also consider other causes such as:

• Drugs: e.g. morphine (causes release of ADH and direct urinary retention)
• Endocrine: SIADH
• Metabolic: hypoxaemia (increases ADH secretion)
• Misc: Pain and nausea (both increase ADH secretion)
• Urological: outflow obstruction e.g. prostatic hypertrophy with acute retention, bilateral ureteric obstruction from malignancy

Please refer to a standard textbook for the extensive list of causes. The above are merely examples to consider.

Hence, when assessing a basic thing such as urine output, we come back to basics. History and physical examination.

Looking at the laboratory studies can tell us further information e.g. worsening BUN and creatinine levels. Such lab results with an examination consistent with hypovolaemia tells us that the patient needs more fluid and not diuretics.

Normal laboratory studies but an examination consistent with hypovolaemia and low urine output should still prompt us to give more fluid.

On the other hand, a hypervolaemic patient may have laboratory studies indicating liver disease, cardiac failure (raised BNP) etc. These can guide us to a more precise diagnosis. Sometimes, such patients have existing renal dysfunction and so the cautious and judicious use of loop diuretics can be considered.

Remember that in acute renal failure, a meta-analysis of 9 studies in adults with ensuing or actual acute renal failure showed no benefit with the use of frusemide and in fact, caused ototoxicity (BMJ 2006;333:420-3)

If you are concerned about causing heart failure (a topic I have touched upon several times in the past) a fluid challenge of 250ml 5% dextrose can be given stat. One can then reassess the circulation for blood pressure, rise in the JVP (or CVP), pulmonary crepitations and improvement of urine output.

If urinary retention is considered, a renal tract ultrasound is quick, non-invasive and provides valuable information. Please don't jump for the contrast CT as contrast nephropathy can ensue.

Examination of the urine may reveal white cells, red cells, casts etc, that can point you towards an intrinsic renal problem rather than pre- or post- renal cause.

So, in summary, please fully assess your patients. Don't go for the easy option of giving frusemide to increase the urine output as you may just end up with a worse problem ! Get out of the habit of knee jerk frusemide and use the grey matter you have been given instead.

Please consider.....

Can you be truly paperless? Yep!!

Dear Bloggers

As you probably have already guessed, I love technology! At the same time, I like to promote the traditional values of medicine and the basic principles and practice on which medicine was built. This seems kind of strange doesn't it; almost at the extremes of the spectrum of old and new but hey, that's me!

One thing that causes immense problems is the build up of medical papers on my desk and the inability to carry all of those papers around and to access them just when you need to.

However, I have found a way to be entirely paperless and still be able to access all of those papers!

Yep is a software package for the Apple Mac that scans your Mac hard drive for all PDF documents and organises them into a logical list for searching and viewing. It does far more than that! It allows you to scan pages and creates PDF files so that you can keep all of those medical papers with you on your laptop! It does this within the software itself. The PDFs can be tagged as well. Great!!

When displaying the files, they are projected full screen just as if you were reading the hard copy.

Of course, you also need a flatbed scanner to get the most out of the software!

The software is free to use for 21 days afterwhich, should you wish to continue using it, you must purchase it. It is inexpensive in the grand scheme of things and will make your life so much more liveable with all that extra space created with no paper getting in the way. :-)

This means having a clear desk, easier access to information, portability and organisation!

If you are interested in this software then please check out the Yep website.

With all those papers now as PDF files, they can be transferred to your PDA such as your Palm Pilot, WM5/6 smartphone, Blackberry, iPod Touch or iPhone. Another good piece of software for rendering PDF files fully viewable on the Palmpilot, WM5/6 or Blackberry devices is the Repligo software by Cerience. This reformats PDF files and allows full view or just the text to be displayed in flowed format. Moreover, it will also allow you to highlight the text in different colours. The conversion / viewing software will only work on a PC running Windows - not Mac (boo hoo).

If of course you are ultra-mobile with a smartphone having a data plan that allows cheap heavy data use, you could upload all of your PDF files to the 'internet cloud' e.g. MobileMe, GoogleDocs etc. There are several programmes availble on the iPhone that allow just this kind of access and it can save you time, smartphone memory and avoid having to lug around a laptop. The viewing experience on a smartphone is not great compared to a laptop / desktop machine but for quick access and mobility it seems to be the way that a lot of people are now choosing for access of information.

If you have any solutions to avoid the paper and killing of the world trees then please drop me a line and get published!

Christmas will soon be here and then the New Year. I will try and keep the blog articles going during this busy time, so drop in from time to time -- but I am sure you have better things to do :-)

December Case: The Long Awaited Answers

Dear Bloggers

Thank you for waiting. This case is very difficult and it would be the kind of grey-case that one would be given in the UK Membership examination (MRCP). In such exams, only the relevant data is provided with much focus on the history and physical examination with some basic radiology and salient, albeit selective laboratory data to give hints but not to lead the doctor directly to the answer. To give all the studies to you would have made the case more easy to answer but would not have been such a challenge. Nevertheless, from the information provided, it should at least have given you some clues as to what was happening in this patient.

Dr Keita Tatsuno, Department of Infectious Disease, Tokyo University, Japan has kindly sent in his answers to the case as follows:

Very interesting and difficult case. I try to answer, but please forgive me not in order. First, I guess the valve is mitral valve. Because the pansystolic murmur suggest the regurgitation. If the murmur were associated with ejection, the climax of sound would be at mid contracting phase. And the radiation to the left axilla fit in the direction from left ventricle to left atria.

Second, the subsequent loss of consciousness suggested another etiology than MSSA bacteremia. Usually, it might be typical pattern to suspect the embolic event in central nervous system, especially in acute infective endocarditis case. Of course, still there is some possibility of too early CT imaging study and need to check the MRI image. But in this case, it is not typical for emboli that the neurological abnormality ranged from loss of conscious to decreased muscle tone. I want to think such etiology as low blood glucose, hyponatremia, drug, hypothyroidism and so on, which affect all of the central nervous system including reticular activating system.

I want to check up these problems primarily, i.e. sodium, calcium, pH (arterial blood gas), glucose, serum creatinine. Especially, I am curious about sodium level. Because you mentioned she had very high urine osmolality. These sound suggesting SIADH.

Dr Stein, Florida, USA, has kindly provided answers to the case as follows:

1. Valve: Mitral-regurgitation
2. Hypoperfusion of kidneys and brain from hypovolemia and or relative hypotension [pseudo-normalization in hypertensive pt] from distributive (vasodilatation) near shock from sepsis. Cold extremities and modest tachycardia may be marker for vasoconstriction. If tent sign = extensor skin remaining up when lifted up, that is unreliable in elderly who have + sign from loss of elastic tissue. Axillary sweat absence may be indeterminate for volume status in septic patient. Another possibility is septic emboli from mitral valve to brain such as vertebral artery system to mid-brain system. Also electrolyte abnormalities such as hyponatremia may account for deterioration. She entered in hemocontrated and hypovolemia state. High urinary osmolality might indicate SIADH. However SIADH can only be diagnosed in normo-volemic state.
Another aspect is the acute IE on assumed diseased mitral valve causing acute valve perforation and acute pulmonary edema. Rarely hypothyroid and adrenal insufficiency may co-exist or exacerbate from the IE septic state. 3. Neuro involvement includes diffuse higher cortical dysfunction as found in hypoperfusion, sepsis and metabolic derangements all of which this patient had. I teach not to use the term `Dolls eyes positive.` What does this mean in simple English?: dolls eyes present(+) which is normal brain stem response or dolls eyes abnormal which is brain stem dysfunction(+sign). Hence Positive/+ has 2 opposite meaning. To avoid both inter/intra/transcultural confusion, only normal(present) or abnormal(absent) is required to avoid your Brit and US confusion. Do not depend on `tradition` to avoid this pitfall.

4. Fluid challenge/resuscitation. Follow hourly urine output increases with bolus and high DIV infusion guarding for heart failure, follow cardiac ECHO for valve perforation. Also repeat brain CT if suspect brain septic emboli.

5. See above

Hirotaka Kato, a 6th-year-student of Kumamoto University has provided an answer to the case.

Q1. Which valve is affected by the confirmed endocarditis?
Mitral valve. Radiation to axilla and becoming louder during expiration are suggestive.

Q2. What is the likely etiology of the other cardiovascular clinical signs and the loss of consciousness?
#1 hypovolemia
#2 sepsis
From the first physical exam, hypovolemia came up to my mind first. Tachycardia, slightly low blood pressure, cold fingers and dry membranes indicate that. Despite of IV fluid + antibiotics administered, the patient has been worsening, however. To me, high Hb/Ht and a high urine osmolality keep the possibility of hypovolemic state. And also, sepsis should be considered in this case, I think.

Q3. Which part of the nervous system has been affected?
Given areflexia and hypotonia, the cerebellum or neuromuscular junction or muscles can be considered.
In this patient who is likely to have the DIC state (or CNS infection possibly), the cerebellar involvement is most likely.
Neuromuscular junction (Lambert-Eaton) is also considered, but less likely now because malignancy cannot unify the symptoms.

Q4. What would be your next test?
1 physical exam. - vital sign + Is there now no edema?, cold extremities?, dry membrane?, no skin rash?
2 Blood test - Cr, BUN, Na, K, Ca, Glucose, NH3, Blood smear

Q5. What might be the cause of the neurological condition present?
Head CT and CSF analysis didn't show any abnormalities! I would like to list two as the possible causes.
1. septic or hypovolemic shock leading to hypoxia in the brain especially the cerebellum
2. shock + paraneoplastic syndrome.

Dr Yosuke Ebisu of Kameda Hospital, Chiba, also provided a reply to the case.

I read your blog. It is interesting case!! I think like that.

(Problem lists)

#1 fever

#2 obtundation

#3 Cheyne-Stokes respration

#4 oliguria

#5 splinter hemorrhage

(assessment)

# endocarditis caused by MSSA

Now you have treated it with fluoroxacillin and gentamycine. After that the patient became gradually obtundation,and her urine output decreased.

Then I think three passibilities.First,it is heart failure caused by destruction of the mitral vulve.It is because HF cause reduction of effective blood flow and then oliguria occur. Then the blood flow of medulla reduce, it cause Cheyne-stokes respiration.

Second,renal toxicity of gentamycin.It cause oliguria and if it became severe,the patient may have uremia. Then her consciousness will be impaired.

Third, septic emboli. It cause cerebral infarction. According to your blog, her extremities were flaccid and doll's eye movement was intact. So I suspect infarction of medulla.(Cheyne-Stokes respiration support this.)

(Plan)

-check heart sound(S3,S4),JVD and edema

-echo cardiogram: check the valve.(If the valve is destroyed we should think operation soon.)

-blood test,especially Cre and BUN.(If renal function decrease, we shoud change the drug or it's dose.)

-Head MRI

Here is the answer from Professor Matsumura, Kanazawa University of Medicine.

Thank you for showing me an interesting case.
I will try to make my hypothesis.

Questions: 1) From the physical examination, which valve is affected by the
confirmed endocarditis?

This case showed classic features of acute infective endocarditis. There
were several splinter haemorrhages in the nails and Janeway lesions on the
palms.
Cardiac examination disclosed Levine II/VI pansystolic murmur in the APEX
area radiating to the left axilla accentuated on expiration.
Vegetation must be on the mitral valve.

2) From the history and first physical examination, what is the likely
aetiology of the other cardiovascular clinical signs (excluding those of
endocarditis) and the subsequent loss of consciousness?

This patient had high fever. I suspect that this patient had volume
depression and pure water deficit following findings. Cold finger and toes,
Pulse 100/min regular, BP 100/80, JVP not raised, dry skin, dry mucous
membranes, tenting sign positive, no axillary sweating.

3) With the follow-up neurological examination in mind which part of the
nervous system has been affected?

This is the most difficult question of this patient.
I would make problem list.
#1 Altered mental status, deep coma
#2 Doll's Eye sign positive
#3 Tone diffusely decreased
#4 Areflexia
#5 Cheyne-Stoke respiration
#6 Anorexia
#7 Oliguria
#8 Pure water deficit and volume depression (Hb 18, haematocrit 0.5 and a
urine osmolality of 1000)

I have to differentiate the cause of #1 altered mental status first.
Mnemonic of altered mental status is AIUEOTIPS,“あいうえおちっぷす” in
Japanese.

A：Alcohol, not likely
I：Insulin（hypo/hyper‐glycemia）
U：Uremia
E：Encephalopathy（hypertensive, hepatic）, not likely, Endocrinopathy
（adrenal, thyroid）, not likely, Electrolytes（hypo/hyper‐Na, K, Ca, Mg）
O：Opiate , not likely or other Overdose, not likely，decreased O2
（hypoxia, CO intoxication
）
T：Trauma, not likely, Temperature（hypo/hyper）
I：Infection（CNS, sepsis, pulmonary）
P：Psychogenic, not likely, Porphiria, not likely
S：Seizure, not likely, Shock, Stroke, not likely, SAH, not likely

In case with endocarditis, septic emboli is the common cause of neurological
problem. But head CT disclosed no abnormalities. #2 Doll's Eye sign positive
indicates that the brain stem of this patient was intact.
#3 Tone diffusely decreased and #4 areflexia indicated PNS and/or muscle
problem, not the problem of upper motor neuron. #5 Cheyne-Stoke respiration
can indicate bilateral forebrain disease or diffuse bihemispheric disease,
Cheyne-Stokes respiration is now known to occur with unilateral hemispheric
and brainstem infarcts (UpTo Date).
It is difficult to point out the one part of neuro-anatomical problem of
this patient.
Hypo/hyper‐glycemia, uremia, or hypo/hyper‐Na, K, Ca, Mg should be
differentiated.

4) What would be your next test to confirm your suspicions?
I want to know following test.
Na, K, Cl, Ca, Mg, BUN, Cr, glucose, serum OSMO, blood gas analysis.

5) What might be the cause(s) of the neurological condition present?
My most likely diagnosis is hypernatremia, hyperosmolality. Serum sodium
must be high more than 160 meq/L. And BUN and serum creatinine must be high
level too.

Izumi Nakayama, 6th year medical student of Osaka University named the correct diagnosis below.

.... I tried this month's case on your blog. It is the first time to send you my answer.

My answer for the December case...

Questions: 1) From the physical examination, which valve is affected by the confirmed endocarditis?
1. Mitral regurgitation sound. (it is common but accentuation on expiration is unusual for the left side heart murmur, isn't it? )

2) From the history and first physical examination, what is the likely aetiology of the other cardiovascular clinical signs (excluding those of endocarditis) and the subsequent loss of consciousness?
Her dry skin, dry mucous membranes indicate she had been dehydrated.
I'm sorry but I don't know 'the tenting sign'. What is it like?
1. brain stem infarction. small thrombi from mitral vulve.(dehydration increases the risk of thromboembolism.)
2.central pontine myelinolysis (although chronic hyponatremia is not likely because she had been dehydrated. I don't know CPM can occur in rapid adjustment of dehydration or hypernatremia.).
.
3) With the follow-up neurological examination in mind which part of the nervous system has been affected?
positive Doll's sign and generalized weakness indicate the lesion either in the midbrain or in the pontine.

4) What would be your next test to confirm your suspicions?
MRI including brain stem. repeat neuro exam. plasma sodium concentration, plasma osmolarity, .
5) What might be the cause(s) of the neurological condition present?
same as question 2.

My impression is like above. First I came up with the infarction. But I think it cannot explain her gradual declining.

Many thanks for the excellent opinions sent in this month.

Now, let's go through the answers.

1) From the physical examination, which valve is affected by the confirmed endocarditis?

This patient has a pansystolic murmur in the left apex which radiated to the axilla. It is accentuated by expiration which makes it a left sided cardiac murmur. By definition, pansystolic murmur in the aforementioned location and attendant features would suggest mitral regurgitation.

2) From the history and first physical examination, what is the likely aetiology of the other cardiovascular clinical signs (excluding those of endocarditis) and the subsequent loss of consciousness?

The other cardiovascular signs include cold hands and feet (suggesting peripheral vasoconstriction), tachycardia, low blood pressure, tenting of the skin and absent axillary sweating are all consistent with hypovolaemia e.g. as a result of dehydration.

The tenting sign is procured by lifting a piece of skin with the examiners finger tips to produce what looks like an upside down V sign or what is commonly referred to as a 'tent'. In a patient with normal skin elasticity, if there is normal hydration, the skin should immediately retract to its normal flat position. In the presence of dehydration, the skin takes longer to return to the normal position producing a positive sign. However, in the elderly who have loss of elastic tissue, the sign can be falsely positive. Although the tenting sign is usually performed on the dorsum of the hand or forearm (extensor surface), the best place to check for tenting sign in the elderly is the inner thigh.

3) With the follow-up neurological examination in mind which part of the nervous system has been affected?

This patient had a completely normal nervous system examination on admission. However, the follow-up examination produced a picture that should have been interpreted as generalised flaccidity, generalised areflexia and indeterminate Babinski suggesting either an acute brainstem or diffuse cerebral injury. However, with the presence of Cheyne-Stoke respiration and positive Doll's eye sign* (abnormal), a brainstem lesion would be highly suspected. However, as we ascertain from the physical examination, the pupillary reflexes are normal suggesting that it does not completely involve the midbrain. That leaves the possibility of the medulla oblongata and pons being affected.

*note: I take heed of Dr Stein's advice and agree about positive / negative aspect that can cause confusion in respect of the Doll's Eye sign. It is probably better to describe what is seen so that everyone can understand whether the sign is present or not rather than as I originally described it. Apologies. Thank you Dr Stein for the very constructive advice.

With a normal CT brain examination, cerebral oedema would seem less likely and a significant structural brain lesion in the cerebral hemispheres would be ruled out, as would bleeding. It is unfortunate that the opening pressure of the CSF was not measured in this patient which is the usual way for understanding if raised intracranial pressure is truly present rather than just relying on a seemingly normal CT scan.

Infarction might be less easy to rule out especially in acute neurological deterioration and particularly when concerning the brainstem and cerebellum which are difficult to image accurately on CT. As this patient has confirmed endocarditis, one would naturally suspect multiple embolic infarction although other diagnoses should also be entertained such as global ischaemia, metabolic or endocrine causes as rightly mentioned by several of the above physicians and students.

4) What would be your next test to confirm your suspicions?

An MRI of the brain and brainstem with the addition of vascular views.

Although measuring the serum osmolality is useful, the physical examination tells us that this patient already has a high osmolality and moreover, it can also be calculated from the serum electrolytes. I see that formerly measuring it might be useful as a guide to know how quickly it is recovering but in reality, one follows the patient's conscious level, hydration status and basic serum electrolytes to know that.

Measuring the glucose (hypoglycaemia / hyperglycaemia) would be correct -- it was normal.

An ABG would be reasonable and in hypovolaemic states, one might see a rise in the serum lactate (lactic acidosis) and renal impairment would also contribute to a metabolic acidosis. Urine ketones would be useful to establish if there was a DKA present (not in this case) and remember that starvation can raise the ketones.

5) What might be the cause(s) of the neurological condition present?

The patient has confirmed endocarditis. Hence, an embolic source leading to brainstem infarction might realistically be the cause of the brainstem abnormality. However, we are told that the patient has history, physical examination and basic lab studies consistent with severe dehydration.
In respect of Dr Stein's comments, he is correct in saying that SIADH can only be diagnosed in a patient who is normo-volaemic. Hence, with concentrated urine being present in the context of hypovolaemia / dehydration, then this would be Appropriate ADH secretion rather than inappropriate secretion.

Severe dehydration is a risk factor for hypernatraemia and haemoconcentration. Hypernatraemia can result in brainstem abnormalities such as Central Pontine Myelinolysis (as can hyponatraemia with rapid correction) and haemoconcentration can cause cerebral vein thrombosis.

What happened next?

The MRI scan of the brain is shown below. As can be seen, the brainstem shines like a beacon as do the basal ganglia. This patient indeed had severe pre-renal failure with severe uncorrected hypernatraemia (max 170mmol/L), high BUN and creatinine for several days due to dehydration, which when corrected, was done so over 3-4 days, making the rare diagnosis of Severe Central Pontine Myelinolysis as the top diagnosis here.

The T2 'Flare' MRI pictures below demonstrate central pontine plus extra-pontine involvement in the basal ganglia, the cerebellum and its peduncles. Thank you Dr Y.


Given the fact that the CSF examination was normal goes against a CSF bound infectious aetiology for cause of the brainstem problem. Moreover, embolic phenomena were considered but the arterial views of the MRA were within normal limits. In addition, the changes of the brainstem and basal ganglia are symmetrical with no diffuse cerebral involvement making symmetrical, selective embolic impaction very unlikely. Of course, a brainstem glioma should be considered but with the over-riding history of this patient, the rapid deterioration and a previously normal CT scan makes this diagnosis somewhat remote.

Hypernatraemia is a rare cause of central pontine myelinolysis. It usually occurs in the context of hyponatraemia with the over-rapid correction of the sodium.

After a Medline Search, please see the following interesting cases below:

J Intensive Care Med. 2006 Nov-Dec;21(6):372-6. Links

Osmotic demyelination and hypertonic dehydration in a 9-year-old girl: changes in cerebrospinal fluid myelin basic protein.

Shah B, Tobias JD.

University of Missouri School of Medicine, Columbia, MO 65212, USA.

A 9-year-old girl was admitted for the treatment of hyper-natremic dehydration. Her history was significant for psychogenic polydipsia, hyponatremia, and a renal concentrating defect. She presented with a 2-day history of altered mental status, ataxia, lethargy, fever, nausea, vomiting, and diarrhea. Meningitis was ruled out. Over the course of her illness, slow rehydration was maintained with a gradual decrease (10 mEq per 24 hours) of the serum sodium. Despite this care, she developed quadriparesis, and magnetic resonance imaging performed on day 6 of her illness was consistent with osmotic demyelination (central pontine myelinolysis). To rule out an excessively rapid correction of hypernatremia as the etiology of the problem, a myelin basic protein was measured in the cerebrospinal fluid that had been obtained on hospital day 1. The myelin basic protein was 649.50 ng/mL (normal, 0.07-4.10 ng/mL). The current literature is presented regarding the postulated pathogenesis of central pontine myelinolysis and suggested therapies, previous reports of central pontine myelinolysis in children are reviewed, and the potential role of myelin basic protein in its diagnosis is discussed.

Presse Med. 1999 Jun 12;28(21):1112.Links

[Central pontine myelinolysis following correction of hypernatremia in an aged patient]

[Article in French]

Bour-Guichenez G, Savin D, Moulaire V, Lalu T, Capieu L, Jonquet O.

Rinsho Shinkeigaku. 1994 Nov;34(11):1130-5.Links

[A case of central pontine myelinolysis and extrapontine myelinolysis during rapid correction of hypernatremia]

[Article in Japanese]

Go M, Amino A, Shindo K, Tsunoda S, Shiozawa Z.

Third Department of Internal Medicine, Yamanashi Medical College.

A 69-year-old woman was admitted because of severe dehydration due to anorexia. Consciousness disturbance was found to be due to severe abnormalities of serum electrolyte balance, but recovered quickly by correcting the hyperosmolality. While the initial serum sodium value of 186 mEq/L was corrected to 139 mEq/L in 5 days, locked-in syndrome, bilateral hand tremor and tetraparesis appeared. Brain magnetic resonance imaging (MRI) revealed symmetrically high signal intensity areas on T2-weighted images and low signal intensity areas on T1-weighted images in central part of pons and bilateral middle cerebellar peduncles. One and a half month later, these neurologic symptoms were improved and the MRI abnormalities also disappeared. Auditory brain stem responses which showed prolongations of III to V wave peak to peak latency at the onset returned to normal. It is noted in this case that central pontine myelinolysis (CPM) and extrapontine myelipolysis (EPM) appeared during the period of rapid correction of hypernatremia. Although it is known CPM and EPM are caused by hypernatremia or the rapid correction of hyponatremia, there has been reported only one case of CPM and EPM after rapid correction of hypernatremia. According to the hypothesis of Norenberg, rapid rise in serum sodium may cause CPM and EPM, but if CPM and EPM are caused by the rapid correction of hypernatremia in this case, CPM and EPM may be caused by another pathogenesis of the disorder.

As can be appreciated from the above case reports, it can occur in all age groups. In its severe form, it can result in tetraparesis, pseudobulbar palsy and hence, a locked-in syndrome. There is a high risk of death in such patients; 5-10% beyond 6 months.

This problem occurs due to release of myelotoxic compounds resulting in destruction of myelin sheaths with the preservation of neurones and axons. Such patients can be found to have a raised Myelin Basic Protein in the CSF.

Hypernatraemia and Hyponatraemia

Severe hypernatraemia can be avoided- The patient presented with signs of hypovolaemia which worsened during the hospital admission, and as a result, appropriate fluid management to ensure the return of normal circulation and electrolyte balance would have gone some way to reverse this situation.

There is a commonly held view that patients should not be over-hydrated because of the fear of causing heart failure. This is an unfortunate opinion. Patients with mismanaged circulation die from renal failure and may develop problems such as coagulation abnormalities e.g. DVT, PE, cerebral and renal vein thrombosis and hypernatraemia. Signs of dehydration / hypovolaemia and pre-renal impairment suggests a generalised tissue hypo-perfusion state and therefore, it tells us that the patient needs more circulation and hence, more water and / or blood.

Of course, over vigorous hydration can in some instances result in pulmonary oedema especially if there is an impairment of cardiac or renal function. However, pulmonary oedema is much more manageable than renal failure. Fluid overload responds to drugs such as furosemide, nitroglycerine and if need be, CPAP can be used to push the fluid out of the lungs. In the worst case scenario a patient with pulmonary oedema and or renal failure can utilities haemofiltration or dialysis respectively (if necessary and if available). Of course, diuretics will only work well if the kidneys were previously normal and have a sufficient circulation and hence we come back to the use of appropriate fluid to replenish the renal blood flow.

In such a patient, central venous pressure monitoring / JVP measurement would be beneficial to help guide the fluid administration plus repeated examination of the chest for crepitations (crackles).

Conversely, if the patient has developed a severe hypernatraemia or hyponatraemia, then the correction of the sodium should be done more slowly e.g. 10-12 mmol/24 hours. However, if the patient is shocked and in pre-renal failure such fluid might have to be administered more quickly. However, the type of fluid given is very important. Opting for 5% dextrose in severe hypernatraemia can cause rapid shifts in Na-H20 and should initially be avoided. Most practitioners would start with normal saline (0.9%) which is still nevertheless hypo-osmotic when compared to the serum hyper-osmotic state. This leads to a more gradual reduction in Na level. If the serum Na does not start to correct despite the use of normal saline then half-normal saline (0.45%) can be considered but regular monitoring of Na should be ensured so that an over-rapid correction of the Na does not occur.

So remember, it is not only over-rapid correction of hyponatraemia that can cause central pontine myelinolysis, by also the development of hypernatraemia or its over-rapid correction too !

This brings me back to a salient point that I have mentioned on numerous occasions over time, examine your patients! List the problems of the history, physical examination, labs and radiology. Aim to interpret the features and group them together and try to form a hypothesis for different potential scenarios e.g. IE -> embolic infarction, brainstem signs in dehydrated/hypovolaemic patient -> ? hypernatraemia ? hypoxaemia ? cerebral vein thrombosis etc... When doing the physical examination, look for the signs of dehydration (as above), check the urine output (place a Foley catheter and measure the hourly urine production) and serum renal function and use enough fluids to correct the circulation.

Hypernatraemia with raised BUN and Creatinine usually signifies a reduced oral intake of fluid or that the patient is not producing or reacting to Vasopressin (Diabetes insipidis). The latter two are unusual causes but should be investigated if the circulation fails to improve with vigorous fluid correction. The clue that this was dehydration rather than diabetes insipidis was the highly concentrated urine suggesting appropriate ADH activity whereas in the latter disease, the urine is dilute because of failure to concentrate the urine. This could not have been consistent with SIADH as described above.

Thank you ever so much for such great contributions to this month's case. It was certainly a tough one.

Moreover, I look forwards to more challenging case to present to you into 2009 and beyond. Please keep coming back to the blog when you get the chance.