Chronic fatigue syndrome, wernickes, Narcolepsy

Question 1

What is the definition of CFS/ myalgic encephalomyelitis (ME)

Answer 1

is a long-term condition that can affect different parts of the body. The most common symptom is extreme tiredness. The cause of ME/CFS is unknown.

Question 2

What is ME classified as?

Answer 2

classified under diseases of the nervous system in the SNOMED CT and ICD10

Question 3

What are the key diagnostic features of ME/CFS

Answer 3

• Post-exertional malaise/symptom exacerbation
• Activity-induced muscle and brain fatigue
• Cognitive dysfunction
• Unrefreshing sleep pattern may include hypersomnia (i.e excessive sleep requirements) in the early post-infection stage, fragmented sleep and myoclonic movements, or restless legs syndrome, later on
• Autonomic nervous system dysfunction/dysautonomia involving orthostatic intolerance - an inability to sustain physical or mental activity whilst standing.
  can produce symptoms such as lightheadedness, feeling faint, blurred vision,
• Pain
• Poor temp control
• Flu like symptoms
• Intolerance to alcohol or increased sensiticty to drugs and alcohol
• Headaches
• Sensory disturbance
• Digestive disturbances

Question 4

Mild ME/ CFS

Answer 4

people with mild ME/CFS care for themselves and do some light domestic tasks (sometimes needing support) but may have difficulties with mobility. Most are still working or in education, but to do this they have probably stopped all leisure and social pursuits. They often have reduced hours, take days off and use the weekend to cope with the rest of the week.

Question 5

Moderate ME/CFS

Answer 5

people with moderate ME/CFS have reduced mobility and are restricted in all activities of daily living, although they may have peaks and troughs in their level of symptoms and ability to do activities. They have usually stopped work or education, and need rest periods, often resting in the afternoon for 1 or 2 hours. Their sleep at night is generally poor quality and disturbed.

Question 6

Severe ME/CFS

Answer 6

people with severe ME/CFS are unable to do any activity for themselves or can carry out minimal daily tasks only (such as face washing or cleaning teeth). They have severe cognitive difficulties and may depend on a wheelchair for mobility. They are often unable to leave the house or have a severe and prolonged after-effect if they do so. They may also spend most of their time in bed and are often extremely sensitive to light and sound.

Question 7

Very severe ME/ CFS

Answer 7

people with very severe ME/CFS are in bed all day and dependent on care. They need help with personal hygiene and eating, and are very sensitive to sensory stimuli. Some people may not be able to swallow and may need to be tube fed

Question 8

What should we be aware of when it comes to ME/CFS

Answer 8

is a complex, chronic medical condition affecting multiple body systems and its pathophysiology is still being investigated
affects everyone differently and its impact varies widely - for some people symptoms still allow them to carry out some activities, whereas for others they cause substantial incapacity
is a fluctuating condition in which a person’s symptoms can change unpredictably in nature and severity over a day, week or longer
can affect different aspects of the lives of both people with ME/CFS and their families and carers, including activities of daily living, family life, social life, emotional wellbeing, work and education.

Question 9

What is the approach to delivering care for someone with CFS/ME

Answer 9

take time to build supportive, trusting and empathetic relationships
acknowledge to the person the reality of living with ME/CFS and how symptoms could affect them
use a person-centred approach to care and assessment
involve families and carers (as appropriate) in discussions and care planning if the person with ME/CFS chooses to include them
be sensitive to the person’s socioeconomic, cultural and ethnic background, beliefs and values, and their gender identity and sexual orientation, and think about how these might influence their experience, understanding and choice of management.

Question 10

What is estimated for in 1 in 4 adults diagnosed with ME/CFS?

Answer 10

severely affected that they are house-bound or bed-bound, with little functional capacity, needing 24-hour care

Question 11

What is the aetiology and pathogenesis of CFS/ ME

Answer 11

aetiology and pathogenis are unknown (1,2,3,4)
a significant proportion of patients relate the onset of chronic fatigue syndrome to an infection
EBV
Herpes
enterovirus
Hepatitis
Toxoplasmosis
Lyme disease

Question 12

CFS patients show features of what other syndromes

Answer 12

, particularly fibromyalgia and irritable bowel syndrome. This association suggests that these syndromes may share similar pathogenetic, predisposing or trigger factors

Question 13

When should we Suspect ME/CFS

Answer 13

the person has had all of the persistent symptoms * for a minimum of 6 weeks in adults and 4 weeks in children and young people and
the person’s ability to engage in occupational, educational, social or personal activities is significantly reduced from pre-illness levels and
symptoms are not explained by another condition

Question 14

Investigations for ME/CFS

Answer 14

medical assessment (including symptoms and history, comorbidities, overall physical and mental health)
a physical examination
an assessment of the impact of symptoms on psychological and social wellbeing
investigations to exclude other diagnoses, for example (but not limited to):
urinalysis for protein, blood and glucose
full blood count
urea and electrolytes
liver function
thyroid function
erythrocyte sedimentation rate or plasma viscosity
C-reactive protein
calcium and phosphate
HbA1c
serum ferritin
coeliac screening

Question 15

When should you diagnose ME/ CFS in a child/ young person?

Answer 15

Diagnose ME (myalgic encephalitis)/CFS (chronic fatigue syndrome) in a child, young person or adult who has the symptoms as above that have persisted for 3 months and are not explained by another condition

Question 16

What is energy management when it comes to ME/ CFS

Answer 16

is a self-management strategy led by the person themselves with support from a healthcare professional in an ME/CFS specialist team
includes all types of activity (cognitive, physical, emotional and social) and takes into account overall level of activity
helps people learn to use the amount of energy they have while reducing their risk of post-exertional malaise or worsening their symptoms by exceeding their limits
Flexible tailored approach
Long term approach
Not curative

Question 17

When should we refer people with ME/CFS to a physiotherapist or OT working in an ME/CFS specialist team?

Answer 17

If they have difficulties caused by reduced physical activity or mobility or
feel ready to progress their physical activity beyond their current activities of daily living or
would like to incorporate a physical activity or exercise programme into managing their ME/CFS

Question 18

How can we support people with CFS/ ME

Answer 18

Care and support plan
Energy limits
Energy management
Exercise
Flare up treatment
Graded exercise therapy
Physical activity
Relapse

Question 19

Prognosis of CFS/ ME

Answer 19

extremely variable

is estimated that 1 in 4 adults diagnosed with ME/CFS are so severely affected that they are house-bound or bed-bound, with little functional capacity, needing 24-hour care (1)
this can last for months or years. In rare cases, the outcome has been fatal

Question 20

What is the definition of Wernicke’s encephalopathy?

Answer 20

Wernicke’s encephalopathy is a neurological emergency resulting from thiamine deficiency with varied neurocognitive manifestations.

Question 21

What is wernicke-Korsakoff syndrome?

Answer 21

Wernicke–Korsakoff syndrome is the combined presence of Wernicke encephalopathy and alcoholic Korsakoff syndrome.

Question 22

Epidemiology of Wernicke’s encephalopathy?

Answer 22

• M>F
• Wernicke’s encephalopathy has a higher prevalence in patients with a history of alcohol dependence

Question 23

Aetiology of Wernickes encephalopathy

Answer 23

Thiamine (vitamin B1) deficiency

Question 24

RFs of Wernickes

Answer 24

• Alcohol abuse
• Malnutrition
• Anorexia
• Malabsorption due to stomach cancer and IBD
• Prolonged vomiting e.g. due to chemotherapy, hyperemesis gravidarum

Question 25

What is the pathophysiology of Wernicke’s encephalopathy and Wernicke Korsakoff syndrome

Answer 25

• One of the major causes of thiamine deficiency, and therefore Wernicke Korsakoff syndrome, is alcohol abuse. Alcohol leads to decreased thiamine levels in various ways.
  
  • Alcohol interferes with the conversion of thiamine to its active form, thiamine pyrophosphate by blocking the phosphorylation of thiamine.
  • Thiamine is normally absorbed through the duodenum. However, ethanol prevents this absorption process by reducing the gene expression for thiamine transporter-1 within the intestinal brush border.
  • Chronic alcohol abuse can lead to fatty liver or cirrhosis which interferes with the storage of thiamine within the liver.
• Other causes: malnutrition and malabsorption

Question 26

Thiamine deficiency consequences

Answer 26

• Thiamine deficiency impairs glucose metabolism and this leads to a decrease in cellular energy.
• The brain is particularly vulnerable to impaired glucose metabolism since it utilises so much energy.
  
  • If the cerebellum is affected: can affect movement and balance.
  • If the brainstem is affected: can affect motor and sensory innervation to the face and eyes.
  • If the medulla region of the brainstem is affected: can impair the heart rate and breathing
  • Later findings: haemorrhage and necrosis of the mammillary bodies. The mammillary bodies are part of the limbic system which is responsible for memory, emotion, and behaviour.

Question 27

Diff between wernickes and wernicke korsakoff

Answer 27

Wernicke’s encephalopathy is the acute, reversible stage of the syndrome, and if left untreated it can later lead to Korsakoff syndrome, which is chronic and irreversible.

Question 28

S + S of Wernickes

Answer 28

• Ophthalmoplegia: weakness or paralysis of the eye muscles, nystagmus; lateral rectus; conjugate gate palsies
• Ataxia or unsteady gait
• Changes in mental state e.g. confusion, apathy, and difficulty concentrating

May also present with hypotension, hypothermia and reduced consciousness.

Question 29

Wernicke-Korsakoff syndrome

Answer 29

• Mainly targets the limbic system, causing severe memory impairment:
  
  • Anterograde amnesia: inability to create new memories
  • Retrograde amnesia: inability to recall previous memories.
  • Confabulation: creating stories to fill in the gaps in their memory which they believe to be true.
  • Behavioural changes

Question 30

Primary investigations and diagnosis

Answer 30

• Diagnosis is typically made based on clinical presentation
• Bloods including LFTs: measure thiamine levels, measure blood alcohol levels, liver function may be deranged in alcoholism
• Other
  
  • Red cell transketolase test: rarely done, thiamine is a co-enzyme to transketolases so transketolase activity will be low
  • MRI/CT: can confirm diagnosis by showing degeneration of the mammillary bodies
  • Lumbar puncture: to exclude meningitis, encephalitis, and subarachnoid haemorrhage

Question 31

DDs of Wernickes

Answer 31

• Alcohol intoxication
• Alcohol withdrawal
• Encephalitis
• Miller-Fisher syndrome

Question 32

Management of wernickes

Answer 32

• Infusion of thiamine over a few days to get rid of the deficiency, followed by oral supplementation
  
  • Usually given alongside glucose, if hyperglycaemic: it’s important to normalise the thiamine levels first, because without thiamine pyrophosphate, most of the glucose will become lactic acid and that can lead to metabolic acidosis.

Question 33

Complications of Wernickes

Answer 33

• Hearing loss
• Seizures
• Spastic paraparesis
• Coma
• Death

Question 34

Prognosis of WE

Answer 34

If WE is untreated, death occurs in 20% and Wernick-Korsakoff syndrome occurs in 85% of patients.

Korsakoffs syndrome is irreversible and results in patients requiring full time institutional care.

Question 35

What is narcolepsy?

Answer 35

narcolepsy remains an underdiagnosed cause of excessive daytime sleepiness.

Question 36

Pathophysiology of narcolepsy

Answer 36

in narcolepsy there is a disruption in the usual patterns of non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM), or ‘dreaming’, sleep. As a consequence, this causes difficulty in staying asleep and in staying awake and bouts of irresistible daytime sleepiness under unusual circumstances (e.g. while eating or talking) (1)

Question 37

What are some other characteristic features of narcolepsy?

Answer 37

cataplexy (2)
a sudden loss of muscle tone - this feature is provoked by emotional stimuli and which can make the person fall
individuals may have symptoms of cataplexy, in which there is sudden transient loss of muscle tone, typically in response to emotional stimulus
sleep paralysis
unpleasant generalised paralysis - this occurs just before, or while, falling asleep or on waking
vivid hallucinations on falling asleep (hypnagogic) or on waking (hypnopompic)

Question 38

What does narcolepsy affect?

Answer 38

Narcolepsy has a strong genetic aetiology.

is a primary neurological condition affecting hypocretin producing neurones in the hypothalamus
lack of the neurotransmitters hypocretin 1 and 2 (also known as orexin A and B) leads to failure to control sleep and wakefulness

Question 39

How do we get a diagnosis of narcolepsy?

Answer 39

requires assessment in a specialist centre with facilities for multiple sleep latency test (MSLT) and polysomnography and treatment is based on lifestyle modification and the use of wakefulness promoting medications such as modafinil and sodium oxybutate

Question 40

Epidemiology of narcolepsy

Answer 40

There are estimated to be around 1 in 3,000 people with narcolepsy, which typically starts in adolescence or early adult life (1)

the prevalence varies among different populations, being more common in Japan (around 0.16% of the population) and less common among Ashkenazy Jews (around 0.002%) (2)

Question 41

Genetics of narcolepsy

Answer 41

95% of white patients with narcolepsy have the HLA DR2 (HLA DR 15 in the new terminology) genotype.

100% of black patients with narcolepsy have the HLA DQ w1 (HLA DQ w6 in the new terminology) genotype.

The environment may be important because there is only a 25% concordance for narcolepsy in monozygotic twins.

The risk of narcolepsy in first degree relatives of sufferer is 1-2% (a relative risk of 40).

Question 42

What are the 2 approaches to diagnosis:

Answer 42

Both of these:
almost daily daytime sleep episodes for 3 months
cataplexy

4 of the following:
excessive daytime sleepiness or sudden muscle weakness
any of:
sleep paralysis
hypnagogic hallucinations
automatic behaviour
disrupted nocturnal sleep episodes
any of the following polysomnographic features:
nocturnal sleep latency less than 10 min
nocturnal REM sleep latency less than 20 min
mean sleep latency less than 8 min on the multiple sleep latency test (MSLT)
two or more sleep onset REM periods during MSLT
exclusion of medical or psychiatric causation

Question 43

What are the clinical features of narcolepsy

Answer 43

excessive daytime sleepiness:
many patients feel sleepy most of the time
episodically sleep becomes irresistible
after a nap of 10-15 min the patient feels refreshed

cataplexy:
60-90% of patients

hypnagogic and hypnapompic hallucinations:
30-60% of patients

sleep paralysis:
30-60% of patients
The patient my present at any age from childhood to the sixth decade. The peak incidence is between 10 and 20 years. Often patients complain that a change in sleep pattern triggered the disorder.

Question 44

Management for narcolepsy

Answer 44

General advice includes:

adopt a regular sleep routine
avoid excess caffeine and alcohol
If daytime sleepiness continues to be a problem then some patients may prefer to take regular naps.

If naps are not possible then most patients will require drug treatment.

in general, in patients with narcolepsy, treatment is initiated by a specialist
treatments used to increase alertness include dexamfetamine and modafinil, and methylphenidate
concomitant treatment with an antidepressant drug (usually clomipramine) may be given to prevent cataplectic attacks
in practice, management for idiopathic hypersomnia is similar to that for narcolepsy
pitolisant (a wake promoting histamine H3-receptor inverse agonist) may provide a further treatment option (2)

Question 45

When should we refer children urgently for narcolepsy?

Answer 45

refer children with symptoms suggestive of narcolepsy, with or without cataplexy, for neurological assessment or a sleep clinic assessment according to local pathways

Question 46

When should we refer adults with narcolepsy, with or without cataplexy, for neurological assessment

Answer 46

consider referring adults with persistent symptoms suggestive of sleep behaviour disorders (such as agitated or violent movements that are more complex than a simple jerking motion) for neurological assessment.