Myelin Diseases & Nutritional/Metabolic Disorders

Question 1

What are the two types of myelin disorders?

Answer 1

• demyelinating diseases: damage and degradation of normal myelin (ex: multiple sclerosis)
• dysmyelinating diseases: myelin isn’t formed properly (ex: leukodystrophy)

Question 2

What is multiple sclerosis? When does the onset of the disease usually occur?

Answer 2

• MS is a relatively common autoimmune demyelinating disorder characterized by distinct episodes of neurologic deficits separated in space and time; the affected tissue is largely random
• onset usually occurs before age 55

Question 3

Which two major micronutrients can result in CNS disorders when deficient?

Answer 3

• thiamine (B1) and vitamin B12 (cobalamin)

Question 4

Thiamine (vitamin B1) Deficiency

Answer 4

• (this is common in alcoholics; “alcohol amnestic disorder”)
• beriberi disease (systemic)
• Wernicke encephalopathy: abrupt onset of confusion, abnormal eye movements (nystagmus), and gait ataxia
• Korsakoff syndrome: (if prolonged) largely irreversible memory disturbances and amnesia
• together, these are collectively referred to as Wernicke-Korsakoff syndrome
• do NOT give glucose-containing fluid to these patients before giving IV thiamine as a treatment; this may kill them

Question 5

Cobalamin (vitamin B12) Deficiency

Answer 5

• pernicious anemia

- subacute combined degeneration of the spinal cord (combined means it affects both ascending and descending tracts)

Question 6

An average sized brain will consume how much oxygen each minute?

Answer 6

• 250 mL/min

- this equates to 20-25% of the body’s total O2 consumption

Question 7

Which two characteristics of the brain’s metabolic activity make it critically dependent on aerobic and glucose metabolism?

Answer 7

• its rapid metabolic rate (the brain contains tons of enzymes involved in glycolysis and relatively few enzymes involved in gluconeogenesis)
• its lack of stored carbohydrates (liver:muscle:brain = 100:10:1)

Question 8

What’s the progression of hypoglycemic encephalopathy?

Answer 8

• (usually develops when plasma glucose is less than 1 umol/mL)
• confusion –> seizures –> coma –> death

Question 9

What’s the progression of hypoxic encephalopathy? What are two compensatory mechanisms that take place when this occurs?

Answer 9

• impaired vision –> impaired concentration and short-term memory –> lethargy, euphoria, impaired judgement, incoordination –> LOC –> death
• cerebral blood flow can be increased to about twice its normal rate via vessel constriction to increase BP
• cerebral glycolysis will shift to anaerobic metabolism (lactic acid will begin to accumulate now)

Question 10

What is most of the energy in the CNS used for? Why does hypoxic encephalopathy result in all the dysfunction?

Answer 10

• 90% is used to maintain ion membrane potential!
• 10% is used for ATP-dependent enzymes
• hypoxia results in decreased synthesis of ATP (obviously), but also of NTs (especially those derived from the TCA cycle!)

Question 11

Which populations are at a greater risk for developing multiple sclerosis?

Answer 11

• patients with HLA-DR2 (identical twins have 30% chance)
• women (because it’s autoimmune)
• prevalence of MS also increases as you move further away from the equator and with exposure to EBV
• smoking increases progression from RRMS to SPMS

Question 12

What are the three forms of multiple sclerosis? Which is the most common?

Answer 12

• relapsing-remitting (RRMS): most common; months/years pass between episodes of dysfunction without any major lingering deficits once the event remits
• secondary progressive (SPMS): a steady deterioration (no more relapse-remit) after the 2nd or 3rd event (40-45% of RRMS patients shift into this category after 10 years)
• primary progressive (PPMS): least common (15-20% of MS patients); a steady deterioration after the initial event
• (all 3 involve some level of cognitive impairment in most cases)

Question 13

What investigations can be used to diagnose multiple sclerosis?

Answer 13

• an MRI is the best for visualizing the sclerotic lesions
• lumbar puncture (85% of RRMS patients have increased IgG and oligoclonal bands in their CSF, 60% of patients with the progressive disease)
• electrocerebral studies can help with the diagnosis as well
• (note, however, that MS is mainly diagnosed clinically - the investigations are used as support)

Question 14

What is clinically isolated syndrome (CIS)?

Answer 14

• CIS is the first clinical event involving an inflammatory demyelinating lesion (these patients are at an increased risk of developing multiple sclerosis)

Question 15

How do we treat multiple sclerosis?

Answer 15

• there are no treatments to stop the disease progression
• we can manage acute relapses with corticosteroids (methylprednisolone) to hasten recovery
• disease modifying drugs decrease the frequency of relapse: interferon-beta (betaferon, rebif, avonex; lowers cytokine release and alters T-cell function) and glatiramer acetate (capazone; blocks myelin antigen presentation to T-cells)
• immunosuppression and plasmapheresis may help as well
• we can manage symptoms of fatigue, spasticity, neurogenic bladder, impotence, etc.

Question 16

Which deficits do patients most commonly present with during their 1st MS event (CIS)

Answer 16

• clinically isolated syndrome
• 46% present with long tract deficits (sensory or motor)
• 21% present with optic neuritis
• 10% present with brainstem lesion
• 23% present with multifocal lesions

Question 17

Multiple Sclerosis and Pregnancy

Answer 17

• MS’ disease activity actually decreases during pregnancy

- however, it INCREASES during the first 3 months after delivery

Question 18

How many patients with multiple sclerosis remain unimpaired after 10 years? 20 years?

Answer 18

• at 10 years, 50% remain unimpaired (no significant disability)
• at 20 years, 10-20% remain unimpaired (this percentage does NOT include those that are treated)

Question 19

What are the newer drugs used to treat multiple sclerosis?

Answer 19

• (these are 2nd line drugs) monoclonal antibodies
• natalizumab and alemtuzumab
• they have greater efficacy, but have some serious potential side-effects (natalizumab can result in progressive multifocal leukoencephalopathy/PML, especially in patients exposed to the JC virus; alemutuzumab can lead to the development of autoimmune disorders, especially Grave’s disease)

Question 20

In multiple sclerosis, what seems to be the ratio of lesions to relapse?

Answer 20

• 10 lesions for every 1 relapse

Question 21

What is neuromyelitis optica? What else is it known as?

Answer 21

• NMO is AKA Devic’s disease
• this is the demyelination of the optic nerves and spinal cord tracts, behaving similarly to MS
• differentiate from MS via: NMO Ab, bilateral optic involvement (instead of unilateral), increased cell count on CSF (oligoclonal bands are less common here), spinal cord lesions tend to be larger/longer than in MS

Question 22

What is transverse myelitis?

Answer 22

• this is a one-time demyelinating event of the spinal cord
• the targeted area tends to be larger than in MS
• treat with corticosteroids

Question 23

What is acute disseminated encephalomyelitis?

Answer 23

• this is characterized by a diffuse pattern of demyelinating lesions throughout the CNS, but without recurring future events (as would occur in MS)
• mostly seen in children with a viral infection (usually measles or VZV) or following a vaccination (hence, it’s also known as postinfectious encephalomyelitis)
• a more severe event than MS, NMO, or transverse myelitis
• treat with corticosteroids

Question 24

What are leukodystrophies? What is the most common type? What are some others?

Answer 24

• inherited mutations in enzymes involved in myelin production and maintenance
• metachromatic leukodystrophy (most common): mutated arylsulfatase, preventing the degradation of old myelin
• Krabbe disease
• adrenoleukodystrophy: inability to add CoA to long-chain fatty acids; their accumulation damages the adrenal glands and white matter

Question 25

What is the medial longitudinal fasciculus? What can damage it? How will patients present?

Answer 25

• MLF connects the nuclei of CNs III (occulomotor) and VI (abducens) to coordinate certain eye movements
• the MLF can be selectively damaged in multiple sclerosis (it’s one of the many presentations of a relapse)
• patients will present with internuclear ophthalmoplegia (INO); specifically, the patient will only be able to pull one eye to look left/right)
• (to look left, CN VI fires to pull the left eye’s LR and also communicates with CN III via the MLF to pull the right eye’s MR; the patient’s right eye will therefore fail to look left with this condition)
• (to look right, CN VI pulls the right eye’s LR and tells CN III to pull the left eye’s MR; the patient’s left eye with therefore fail to look right)

Question 26

What is subacute sclerosing panencephalitis? What causes it?

Answer 26

• a slowly progressive, debilitating encephalitis that ultimately leads to death (“panencephalitis” means that it affects white and grey matter)
• due to measles virus infection during infancy, with neurological deficits/signs developing years later

Question 27

What is progressive multifocal leukoencephalopathy (PML)? What causes it?

Answer 27

• PML is a rapidly progressive neurological infection of oligodendrocytes leading to death
• occurs in patients with a latent JC virus who then undergo immunosuppression, resulting in reactivation of the virus
• (increased risk associated with natalizumab)

Question 28

What is central pontine myelinolysis? What causes it? What’s the classic presentation?

Answer 28

• the focal demyelination of the pons
• this is of an iatrogenic etiology; due to rapid IV correction of hyponatremia
• classic “locked-in” presentation: paralysis of all voluntary muscles except for the eyes

Question 29

What is the most common demyelinating disorder of the PNS?

Answer 29

• Guillain-Barre syndrome (acute inflammatory demyelinating polyradiculopathy)
• autoimmune reaction against Schwann cells