Demyelinating Diseases -Neurology/IM Flashcards
Definition of Multiple sclerosis
A chronic immune-mediated inflammatory, demyelinating and neurodegenerative disease of the CNS affecting mainly the white matter producing significant physical disability by attacks (relapses) which are the clinical hallmark of MS that occur months or years apart and affect different anatomic locations.
Risk factors of Multiple sclerosis
Age: 20-40
Sex: Females more
Family history: Increase risk
Race: White people
Climate: Temperate climates
Vitamin d: Low levels of vitD or sunlight
Smoking: Active and passive
Infections; eg. Epstein-barr
Autoimmune disease: Thyroid or 1-DM
Clinical picture of MS
Diagnosis of MS requires lesions disseminated in time(two attacks at least 1 month apart) and disseminated in space (two separate symptoms at two separate systems).
a) Onset: most commonly subacute.
b) Course: most commonly remissions and exacerbations i.e. relapsing-remitting MS (RRMS) →A subacute onset (over hours or days) of neurologic symptoms that usually last several weeks then resolve, often leaving few or no deficits.
c) Symptoms and signs:
1) Mentality changes:
- Euphoria. - Depression. - Emotional liability.
2) Speech disturbances (Dysarthria):
- Slurred. - Staccato. - Scanning.
3) Cranial nerves involvement specially:
❖ Optic nerve resulting in:
1) Diminution or loss of vision due to optic neuritis or primary optic atrophy.
2) Pallor of the optic disc specially on the temporal side.
3) Visual field defects (specially central scotoma) and disturbances of colour vision due to selective involvement of the macular fibers.
❖ Oculomotor nerves (3, 4 and 6) resulting in:
1) Diplopia which is a common early symptom.
2) Ophthalmoplegia due to weakness or paralysis of the extraocular muscles.
❖ Facial nerve resulting in:
1) Facial palsy which may be due to an UMNL (common) or LMNL (rare).
2) Hemifacial spasm is rare but if it happens it is pathognomonic of MS.
❖ Cochleo-Vestibular nerve resulting in vertigo which is common in MS. \
4) Motor System affection:
- Monoparesis, paraparesis or less commonly (hemiparesis, quadriparesis or pseudo-bulbar palsy) associated with signs of UMNL i.e. hypertonia, hyperreflexia, +ve Babinski and early loss of the abdominal reflexes.
5) Sensory System affection:
- Transient numbness and paresthesia followed by superficial and/or deep sensory loss.
- Lhermitte’s phenomenon may be present: on flexion of the head there is sudden electric like sensation radiating to the back and limbs, it is due to posterior column involvement in the cervical region.
6) Cerebellar affection:
- Cerebellar ataxia is common (nystagmus, staccato speech, intention kinetic tremor….etc).
7) Autonomic disturbances (common & early):
- Precipitancy, hesitancy of autonomic bladder.
- Impotence. (MS does not affect fertility).
Early findings in MS
1) Lost abdominal reflexes.
2) Sphincteric disturbances and impotence
Characteristic symptoms/sign of MS
1) Lhermitte’s phenomenon.
2) Uhthoff’s phenomenon: worsening of symptoms (e.g. vision) when body temperature is raised (e.g. exercise or hot bath).
Clinical course of MS
1) Clinically isolated syndrome (CIS).
2) Relapsing-remitting (RRMS): 85% of cases. (After 10-15 years, 50-60% of RRMS →SPMS).
3) Primary progressive (PPMS): 10% of cases with gradual accumulation of disability. Average age of onset 40 y. (Males> females).
4) Secondary progressive (SPMS).
Investigations of MS
1) MRI (gadolinium) of brain and spinal cord: It shows multiple white matter lesions (plaques). Enhancement with gadolinium, indicative of BBB breakdown in acute active lesions. Older lesions are non enhancing.
2) Cortical evoked responses: Helps in detection of clinically-silent lesions (Simple, non-invasive and inexpensive)
3) CSF examination:
- Raised IgG index
- CSF-specific Ig Goligoclonal bands (OCBs)
- ↑ Cells during activity up to 40/mm3
- ↑ Total protein content is moderately.
Management of MS
1) Acute relapses:
High-dose Corticosteroids hasten recovery but may not affect ultimate function.
-IV methylprednisolone 1 g daily for 3-5 days.
-Oral methyprednisolone500 mg-2 g daily for 3-5 days.
- Plasma exchange
2) Disease-modifying drugs (DMDs):
-Reduce the frequency of relapses or slow disability progression.
-Injection: Interferon beta-1a
Interferon beta-1b
Mitoxantrone
-Oral: Dimethyl fumarate
Fingolimod
Ocrelizumab
Cladribine
3) Vitamin D3 may have disease-modifying effects in patients and those with high risk for developing MS. recommended dose for patients: 2,000 IU daily.
4) Symptomatic treatment:
▪ Spasticity: Baclofen (PO or intrathecal), Tizanidine, Dantrolene or botulinum toxin.
▪ Bladder dysfunction:
-Even distribution of fluid intake (2 L/day).
-Pelvic floor exercises help urgency and incontinence.
-Drugs: Oxybutynin,Tolterodine, Solifenacin.
▪ Fatigue: Amantadine and Modafinil
