Viva 2

You have been asked to assess a 34-year-old female who has presented with progressive lethargy, malaise and confusion. She has a background of previous morbid obesity and underwent bariatric surgery in the last 6 months with subsequent extensive weight loss. 

She has been intubated for lowered conscious state in the emergency department. On examination she is dehydrated, afebrile with a blood pressure 120/80 mmHg, pulse 118/min, SpO2 99% on FiO2 of 0.3. Prior to intubation she was noted to have bilateral nystagmus.

What is the differential diagnosis?

What specific history or examination findings will you look for?

• The candidate should mention some reasonable questions on history, and specific examination features which relate to their list of differentials
•  

History reveals some recent memory impairment and tendency to "make up stories". Examination reveals signs of heart failure. 

What specific tests would help you narrow your list of differentials?

Any reasonable set will do, eg:

• Biochemistry:
  • Standard panel of bloods, including blood film
  • TFTs
  • Serum cortisol
  • Blood cultures
  • Ammonia level
  • ABG
• Imaging:
  • CT brain
  • Carotid Doppler
• Electrophysiology:
  • EEG

MRI imaging reveals some abnormal signal in the medial thalami, mamillary bodies, tegmentum, and periaqueductal region. How would you interpret these data?

These are the classical MRI findings in Wernicke's encephalopathy and can also be associated with Korsakoff's psychosis. Of course encephalitis and stroke cannot be ruled out.

The only other striking finding on your other investigations is an extremely high ABG lactate, 15.5 mmol/L, with a mild metabolic acidosis (pH 7.30).
How does this change your diagnostic process?

The candidate should focus on the metabolic causes of hyperlactatemia. If not, gently redirect them to this question, by asking:

What are the causes of Type B lactic acidosis, and what associated features would you expect?

Type B1 lactic acidosis, due to a disease state
Malignancy	Tumour markers, LDH (particularly in haematological malignancy and tumour lysis)
Thiamine deficiency	Red cell transketolase
Ketoacidosis /HONK	Blood and urine ketone levels; BSL and serum osmolality
Septic shock	Supportive history, fever, inflammatory markers
Impaired hepatic or renal clearance	Clinical features of ascites, encephalopathy, icterus; deranged LFTs
D-lactic acidosis	D-lactate level, the presence of encephalopathy, history of short gut syndrome
Type B2 drug-induced lactic acidosis
Beta-2 adrenoceptor agonists	Isoprenaline, adrenaline, salbutamol
Metformin	History of diabetes
Isoniazid	History of tuberculosis; seizures responsive to vitamin B6
Cyanide (and by extension nitroprusside)	Aside from cold war spies and malignant hypertension ...History of smoke inhalation
Xylitol, sorbitol, fructose	Consumption of unusual dietary supplements, or use of unusual TURP irrigation fluid
Propofol	Prolonged stay in ICU; infusion rate in excess of 4mg/kg/hr for over 24 hrs
The toxic alcohols eg. methanol	Methanol, formate, oxalate levels.
Paracetamol	Paracetamol levels, history of overdose attempt, and of course LFT derangement
Salicylates	Salicylate levels; characteristic respiratory alkalosis followed by metabolic acidosis
NRTIs (anti-retroviral drugs)	History of Hep C or HIV
Type B3 : inborn errors of metabolism
Pyruvate dehydrogenase deficiency	Specific genetic testing is called for
Electron transport chain enzyme defects	Specific genetic testing
G6PD	Rapid fluorescent spot test detecting the generation of NADPH from NADP

This discussion should take some time. 

Any discussion of red cell transketolase by the trainee should be ceased upon. If they do not bring it up, 

What is the red cell transketolase test, and how is it interpreted?

Red cell transketolase is an enzyme of the pentose pathway which is affected by the presence of thiamine; its activity is decreased in the absence of thiamine (which it uses as a cofactor). Its increased activity with the addition of thiamine in the laboratory (measured by red cell NADH consumption) is used as indirect evidence of thiamine deficiency.

A low transketolase activity along with a >25% rise in activity following thiamine supplementation is diagnostic of thiamine deficiency.

What are the clinical features of thiamine deficiency?

• Encephalopathy
  • Rarely, stupor and coma
  • Most often, confusion and impaired memory
• Ataxia
  • Usually, there are no upper limb or speech cerebelar signs
  • This is because only the anterior and superior vermis are affected
  • The lower limb cereballar signs conspire with vestibular damage and thiamine-associated polyneuropathy(i.e. "I can't feel my legs").
• Eye signs
  • Nystagmus is the most common (it is usually horisontal)
  • Conjugate gaze palsies
  • CN VI (lateral rectus) palsies (bilateral)
  • These are due to lesions of the vestibular and abducens nuclei
• Hypothermia
  • due to impairment of thermoregulation: the hypothalamus is damaged
• Hypotension
  • due to heart failure, "wet Beri-Beri"

What are the clinical features of Wernicke's encephalopathy?

Royal College Criteria Alcoholism, AND one other : Acute confusion Decreased level of consciousness Memory problems Ataxia Ophthalmoplegia Hypothermia with hypotension

European Federation of Neurologic Societies Any two of: Dietary deficiencies Eye signs Cerebellar signs (ataxia) Either altered mental state or mild memory impairment

What are the important elements of management for Wernicke's encephalopathy?

• The treatment consists of some IV thiamine. The college answer to Question 13.3 from the second paper of 2013 suggests 100mg IV daily is a big enough dose. 
• UpToDate recommends the largest dose, 500mg three times a day
• The rationale for such massive doses is the theoretical benefit of producing a steep blood-to-brain thiamine concentration gradient, to facilitate its passive diffusion into the neurons.

The family are anxious to discuss prognosis. What is the most likely outcome for this patient?

• This condition is usually reversible
• If left untreated for a prolonged period, it can lead to Korsakoff's syndrome, which is a chronic condition characterised by memory impairment and confabulation
• According to Flynn et al (2015), "ophthalmoplegia is generally the first symptom to resolve and often reverses within hours to days of starting treatment. Improvement of gait disturbance and mental status change may take 1 or more weeks to resolve".

Disclaimer: the viva stem above may be an original CICM stem, acquired from their publicly available past papers. Or, perhaps it is a slightly altered version of the original CICM stem. Or, it is a completely original viva stem, concocted by the monstrously amoral author of Deranged Physiology for nothing more than his own personal amusement. In either case, because the college do not make the main viva text or marking criteria available, almost everything here has been confabulated. It might sound like a plausible viva and it could be used for the purpose of practice, but all should be aware that it does not represent the "true" canonical CICM viva station.