Neuro - MS and Cerebellar Dysfunctions

A chronic demyelinating disease of the CNS

MS

What areas of the CNS can MS affect?

Cortical, subcortical, cerebellum, spinal cord, and optic nerve

What is the typical age range for MS diagnosis?

20-50 years, with an average age of 31

What are risk factors associated with MS?

Smoking, obesity, and exposure to infectious agents such as Epstein-Barr virus and infectious mononucleosis

What vitamin has been associated with MS relapse rates?

Vit D

What CSF findings are associated with MS?

Elevated immunoglobulins, oligoclonal IgG bands, and slight protein elevation

What do evoked potentials show in MS?

Decreased nerve conduction velocity

Progressive worsening from the beginning with superimposed relapses; progression continues between relapses

Progressive-relapsing MS

Begins as relapsing-remitting MS and then progresses with worsening symptoms, with or without relapses/remissions

Secondary-progressive MS

Continuous worsening without distinct relapses or remissions

Primary-progressive MS

Temporary flare-ups followed by periods without disease progression

Relapsing-remitting MS

Mild disease progression where the patient remains fully functional 15 years after disease onset

Benign MS

A rapidly progressive course leading to severe disability or death soon after disease onset

Malignant MS

What clinical signs can result from spinal cord/corticospinal tract involvement?

Hypertonicity, paresis, and bowel/bladder problems

What can brainstem involvement cause?

Cranial nerve and visual problems

What can cerebellar involvement cause?

Trunk hypotonia and ataxia

What can cerebral involvement cause?

Depression, cognitive problems, paresis, and decreased sensation

What is often the first symptom of MS?

Visual impairment

Is complete loss of a single sensation common in MS?

No. Focal sensory deficits are more common

Neck flexion produces an electric-shock sensation down the spine

Lhermitte's sign

What UMN signs are commonly associated with MS?

Paresis

Spasticity

Increased DTRs

Spasms

Clonus

Babinski sign

Slurred or poorly articulated speech

Dysarthria

Changes in vocal quality, harshness, hoarseness, brethiness

Dysphonia

Difficulty swallowing due to weakness and poor coordination

Dysphagia

Uncontrolled emotion (happy one moment, crying the next)

Lability

Psychosocial Issues in individuals with MS

Depression

Loss of relationships

Loss of roles (family, employment, social)

Financial loss

Loss of Independence

Grieving process may repeat with each exacerbations

What type of tremor is characteristic of MS?

Intention

What is the most commonly reported symptom of MS?

Fatigue

Anther word for global fatigue

Lassitude

What cardiovascular autonomic changes can occur in MS?

Problems with cardioacceleration and reduced BP response during exercise

Spastic bladder vs flaccid bladder

Spastic bladder: Small bladder with failure to store

Flaccid bladder: Large bladder with failure to empty

Increased neurological symptoms in response to heat

Uhthoff's phenomenon

A 0-10 ordinal scale using half-point increments to assess disability in MS

EDSS (Expanded Disability Status Scale )

What systems are included in the EDSS Functional System Scores?

Pyramidal, cerebellar, brainstem, sensory, bowel/bladder, visual, mental, and other functions

Has three subscales: the EDSS with FSS, the Incapacity Status Scale (ISS), and the Environmental Status Scale (ESS) which uses to addresses impairments, disability, and handicap

The Minimum Record of Disability (MRD)

What are the three components of the MS Functional Composite (MSFC)?

Timed 25-Foot Walk (gait), 9-Hole Peg Test (coordination), and Paced Auditory Serial Test (hearing)

What does the MSQOL-54 (Multiple Sclerosis Quality of Life—54) measure?

Quality of life using 11 subscales, including physical health, emotional well-being, pain, energy, social function, cognition, and sexual function

MS Quality of Life Inventory 10 self report scales

Quality of Life

Fatigue

Pain

Sexual function

Bowel and bladder

Visual impairments

Perceived deficits

Mental Health

Social support

Health-related quality of life using 59 items and 6 subscales such as Mobility, Symptoms, Emotional well-being, General contentment, Thinking/fatigue, Family/social well-being

Functional Examination of Multiple Sclerosis (FAMS)

What does the MSIS-29 (Multiple Sclerosis Impact Scale) measure?

The physical and psychological impact of MS

What does the Modified Fatigue Impact Scale (MFIS) assess?

Effects of fatigue on physical, cognitive, and psychosocial functioning

What is the MFIS score range?

0-84, with higher scores indicating greater fatigue impact

What are the three primary goals of PT intervention for MS?

Optimize mobility, maximize physical function, and minimize loss

"Tom's Terrible Triad" for heat sensitivity?

Fatigue + Weakness + Spasticity

What intensity is recommended for MS patients?

Submaximal, approximately 50-70%

What meds are used for pain management in MS?

Carbamazepine, diazepam, gabapentin

Anti-inflammatories

What meds are used for fatigue management in MS?

Ampyra (Dalframpridine) - for motor fatigue

Blocks K+ channels -> ↑s NCV -> improves gait

Provigil - for lassitude

What are major PT interventions for MS?

FMTAs, gait, balance, flexibility, strength, coordination, aerobic conditioning, posture/body mechanics, sensory retraining, wheelchair mobility, seating/positioning, energy conservation, equipment, education, and support groups

What type of stretching is recommended?

Low-load, prolonged stretching

Tom's training triad for heat management and rest

Endurance + Strength + Stretching

What are the 4 P's of energy conservation?

Pacing, Planning, Prioritizing, Positioning

Room temperature

62-68°F

Water temperature is suggested for cooling

Below 85°F

What exercise precautions should be used with MS?

Submaximal training, frequent rest, multiple short exercise routines, and self-monitoring

Aimed at minimizing potential complications, impairments, functional limitations, or disabilities as the disease progresses

Preventative intervention

Modifying tasks, activities, or the environment to allow the patient to remain as functional as possible

Compensatory intervention

Series of occasional clinical, educational, and administrative services designed to maintain the patient's current level of function

Maintenance therapy

What is the primary goal of MS disease-modifying medications?

Slow disease progression

What are the main mechanisms of action of oral MS medications?

Immune suppression, interference with lymphocytic activity, and anti-inflammatory effects

What are the injectable medications listed for MS?

Methylprednisolone

Glatiramer acetate (Copaxone)

Interferon beta-1b (Betaseron)

Interferon beta-1a (Avonex)

Interferon beta-1a (Rebif)

Interferon beta-1b (Extavia)

A family of soluble proteins/cytokines that act as chemical messengers between cells

Interferons

What role do interferons play in the immune system?

Help repair damage and destroy infectious material

What are the three main types of interferons?

Alpha (α), beta (β), and gamma (γ)

Which interferon is beneficial in the treatment of MS?

Beta

Name the oral medications listed for MS.

Aubagio (teriflunomide)

Bafiertam (monomethyl fumarate)

Dimethyl fumarate

Gilenya (fingolimod)

Mavenclad (cladribine)

Mayzent (siponimod)

Ponvory (ponesimod)

Tascenso ODT (fingolimod)

Tecfidera (dimethyl fumarate)

Vumerity (diroximel fumarate)

Zeposia (ozanimod)

What type of medications are the infused MS medications?

Monoclonal antibodies

What is the dosing schedule for Briumvi?

2 initial infusions 2 weeks apart, then every 24 weeks

What is the dosing schedule for Lemtrada?

1 course for 5 days, then 12 months later 1 course for 3 days, then yearly

What is the dosing schedule for Novantrone?

Every 3 months for 2 years

What is the dosing schedule for Ocrevus?

2 doses within 2 weeks, then every 6 months

How often is Tysabri administered?

Every 4 weeks

What is the goal of muscle relaxants used for hypertonicity?

Decrease muscle excitability without limiting muscle function

Which muscles are usually affected by spasticity?

Antigravity muscles such as biceps

Increased muscle tension following injury and inflammation

Muscle spasm

Why does hypertone develop following an UMN lesion?

Due to a decrease in inhibition from the cortex and inhibitory spinal cord interneurons

What medication is primarily used for hypertonicity?

Baclofen

What does tizanidine do?

Acts as a polysynaptic inhibitor within the spinal cord

How does diazepam work?

Acts as a polysynaptic inhibitor and centrally acting drug

Where does dantrolene act?

Directly on the muscle

Where does Botox act?

At NMJ

Muscle relaxant agents that act centrally and can cause a general reduction in CNS activity

Polysynaptic inhibitors

What are examples of polysynaptic inhibitors?

Diazepam

Carisoprodol

Chlorphenesin carbamate

Chlorzoxazone

Cyclobenzaprine

Metaxalone

Methocarbamol

Orphenadrine citrate

What type of receptor does baclofen act on?

GABA-B agonist

What happens when baclofen activates GABA-B receptors?

It causes hyperpolarization → decreased release of excitatory neurotransmitters → increased neuronal inhibition

Where is an intrathecal baclofen pump surgically implanted?

Subcutaneously in the abdomen

What are the three possible intrathecal baclofen delivery patterns?

1. Simple continuous

2. Periodic bolus

3. Complex-continuous

What is the average intrathecal baclofen dose listed?

300-1000 mcg

Where does the catheter enter the spinal canal?

Below L3, then it is advanced to approximately T8-T10

How often may the pump need to be refilled?

Every 1-5 months, depending on pump size, concentration, and dose

Intrathecal Baclofen Candidates

•Moderate to severe hypertonicity

•Potential to be more independent with ADL's

•Non-ambulatory with tone interfering withcaregiving

•Pain or at risk for skeletal deformity

•Committed support system

•Over 4 y/o

•Respond to intrathecal test dose < 100micrograms

•One year post TB

What is the primary mechanism of diazepam in tone management?

Increases GABA's central inhibitory effect at inhibitory interneurons

What is an important characteristic of diazepam?

CNS depressant

Where does dantrolene act?

Directly on skeletal muscle

What receptor/channel does dantrolene affect?

Antagonist of the ryanodine receptor, a calcium-channel receptor in the sarcoplasmic reticulum of skeletal muscle

What type of drug is tizanidine?

Centrally acting α-2 agonist

What is the effect of tizanidine on inhibitory interneurons?

Increases the inhibitory effects of inhibitory interneurons

What does botulinum toxin prevent from being released?

Acetylcholine from presynaptic vesicles

How does botulinum toxin produce its effect?

Binds to the presynaptic axon terminal, is internalized, and inhibits neurotransmitter release

How is botulinum toxin administered for tone management?

Intramuscularly into specific muscles.

How long does the chemical denervation from botulinum toxin last?

Develops within days and lasts approximately 3 months