Multiple Sclerosis (MS) is the most common immune-mediated inflammatory demyelinating disease of the CNS
Affecting both the white and grey matter of the _________________
Clinically it is a heterogenous disease characterized by clinical events disseminated in space and time
brain and spinal cord;
[Clinical Phenotype of multiple sclerosis]
___________ is the most common phenotype, which typically presents in a young adult with a clinically isolated syndrome suggestive of MS:
- Optic neuritis, long tract symptoms, a brainstem syndrome e.g. INO, or a spinal cord syndrome e.g. transverse myelitis
- A relapse in MS is defined as the acute onset of a monophasic clinical episode with symptoms and signs typical of MS for a duration of ____________ preceding a period of clinical stability of at least ___________ and in the absence of fever or infection
5-10% of adult patients have the primary progressive form of MS
- Presents with ___________________
- Most common presentation is a ____________________.
Relapsing-remitting MS (RRMS);
at least 24hours ;
30 days ;
gradual accumulation disability from onset, without superimposed acute relapses ;
spinal cord syndrome with spastic paraparesis
What is Lhermitte sign?
Transient electric shock radiating down the spine or into the limbs after neck flexion
What is Uhthoff phenomenon?
Well-known occurrence in MS where small increases in body temperature can temporarily worsen current signs and symptom
Sign of multiple sclerosis: Fatigue
- Primary MS-related fatigue typically occurs daily and worsens as ______________ Many patients complain of feeling exhausted on waking, even if they have slept soundly
- Acute MS attack-related fatigue may precede the _______________ and persist long after the attack has subsided
the day goes on;
focal neurologic features of the attack
Sign of multiple sclerosis: Visual loss
Optic neuritis is the most common type of visual pathway involvement in MS which results in _______, ________, _______
Presents as ______________ accentuated by ocular movements followed by ___________________
Presence of bilateral optic neuritis is rare in MS and should prompt suspicion of ________________
- Severe optic neuritis + extensive transverse myelitis >3 vertebral segments
- Due to auto-antibodies against _______________
90% of patients regain normal vision over a period of 2-6months after an acute episode of optic neuritis
Reduced visual acuity, positive RAPD, red desaturation;
acute unilateral eye pain;
variable degree of scotoma;
Neuromyelitis Optica (NMO);
AQ4 channels
What are the eye movement abnormalities in a patient with multiple sclerosis?
Abnormalities of conjugate gaze (most common)
- INO
- One-and-a-half syndrome, Dorsal midbrain syndrome
Nystagmus (very common)
- Horizontal/vertical
- Pendular – rare form but specific to MS. Rapid, small-amplitude pendular oscillations of the eyes in the primary position resembling quivering jelly
Abnormalities of slow phase eye movements (common)
- Disordered smooth pursuit
Sensory symptoms
- The most common initial feature of MS and present in almost every patient at some time during the course of the disease
- Sensory symptoms can reflect spinothalamic, dorsal column or dorsal root lesions
- Symptoms include ___________, ________, __________, __________
- Intense pruritus, especially in the ________________, is suggestive of MS
numbness, tingling, coldness, tightness;
cervical dermatomes
What are the motor symptoms of multiple sclerosis?
Paraparesis/paraplegia are more common than isolated upper extremity weakness due to the frequent occurrence of lesions in the descending motor tracts
UMN weakness on physical exam– spasticity in LL > UL, reflexes ++, commonly asymmetrical
Spastic/scissoring gait
Brainstem-related symptoms like dysphagia, dysarthria and respiratory dysfunction can occur in MS though less common
What are the incoordination symptoms seen in patients with multiple sclerosis?
Gait imbalance, ataxia and slurred speech often occur due to cerebellar involvement
Physical findings include: dysmetria, hypotonia, decomposition of complex movements (often observed in UL), scanning speech, ocular dysmetria, truncal ataxia
Symptoms of multiple sclerosis:
Bowel and bladder dysfunction
50% of patients report bowel dysfunction and up to 75% report bladder dysfunction
Extent of sphincter dysfunction often parallels the degree of motor impairment in LL
Neurogenic bladder dysfunction in MS has several underlying mechanisms:
- ________________ : detrusor contraction without urethral sphincter relaxation, leading to _________________________
- Detrusor overactivity (most common abnormality in MS) 🡪 ________________
- Abnormal sensation and detrusor underactivity 🡪 ___________________
_________________ the most common bowel disorders seen in MS
Detrusor-sphincter-dyssynergia (DSD);
functional bladder outlet obstruction 🡪 overflow incontinence ;
OAB/urge incontinence;
overflow incontinence;
Constipation and incontinence
What kind of pain do patients with multiple sclerosis experience?
headache, neuropathic extremity pain, back pain, Lhermitte sign, painful spasms, trigeminal neuralgia,
What is the Mcdonald criteria for the diagnosis of multiple sclerosis?
1) ≥2 clinical attacks
- with ≥2 lesions with objective clinical evidence
- with no additional data needed
≥2 clinical attacks
- with 1 lesion with objective clinical evidence and a clinical history suggestive of a previous lesion
- with no additional data needed
≥2 clinical attacks
- with 1 lesion with objective clinical evidence and no clinical history suggestive of a previous lesion
- with dissemination in space evident on MRI
1 clinical attack (i.e. clinically isolated syndrome)
- with ≥2 lesions with objective clinical evidence
- with dissemination in time evident on MRI or demonstration of CSF-specific oligoclonal bands
1 clinical attack (i.e. clinically isolated syndrome)
- with 1 lesion with objective clinical evidence
- with dissemination in space evident on MRI
- with dissemination in time evident on MRI or demonstration of CSF-specific oligoclonal bands
What is the management of relapse remitting MS?
Acute exacerbations: Glucocorticoids are the treatment of choice (3 to 7 day courses of IV methylprednisolone 500-1000mg daily, with or without a short prednisone taper)
Disease-modifying therapy (DMT)
- Aimed at decreasing relapse rate and slowing accumulation of CNS lesions on MRI
- Infusion therapy with Natalizumab for patients with more active disease and for those who value effectiveness above safety and convenience.
- Injection therapy (Interferons or Glatiramer) for patients who value safety over convenience or efficacy. Intramuscular IFN beta-1a 30mcg weekly or SC glatiramer acetate 40mg thrice a week is preferred
- Oral therapy (Dimethyl fumarate, Teriflunomide, or Fingolimod) for patients who value convenience
How do you manage fatigue in a patient with multiple sclerosis?
Fatigue management class, encourage exercise and activity
How do you manage depression in a patient with multiple sclerosis?
SSRIs, psychiatry/ neuropsychological assessment
How do you manage spasticity in a patient with multiple sclerosis?
Baclofen, tinzanidine, boutulinum toxic injection.
How do you manage pain in a patient with multiple sclerosis?
PT, pregablin, duloxetine
How do you manage sexual dysfunction in a patient with multiple sclerosis?
Oral phosphodiesterase type 5 inhibitors
