Motor Neuron Disease& Neuropathies

Differentiate between Neuromuscular/Functional Weakness

Describe the procedure for Hoover’s Sign:

Procedure:

• Exammer places hand under heel of weak leg and asks the patient to press the heel down forcefully. It appears weak but when the opposite hip is flexed against resistance, downward pressure will be felt under the heel of weak leg

• Discrepancy between voluntary hip extension (which is weak) and involuntary hip extension (which is normal) when the opposite hip is being flexed against resistance suggests functional paresis.

• Hoover sign is thought to be due to crossed extensor reflex to stabilize the trunk/body

When do you suspect degenerative motor neuron disease

pt with:

• Neuromuscular weakness

• No sensory loss or sphincter disturbance

• Progressive course

• No identifiable underlying cause other than genetic basis in familial cases

List the various causes of Motor Neuron Disorders

Causes of Motor Neuron Disorders

• Neurodegenerative

  • Amyotrophic Lateral Sclerosis (ALS)

  • Primary Lateral Sclerosis

  • Progressive Bulbar Palsy

  • Pseudobulbar Palsy

  • Spinal Muscular Atrophy

• Infectious

  • Post-polio, 

  • West Nile virus, 

  • Herpes Simplex Virus [HSV], 

  • HIV

• Immunologic

  • Paraproteinemia [monoclonal gammopathy]

• Drugs and toxins

  • Heavy metals

Describe Amyotrophic Lateral Sclerosis (ALS)

• What is it?

• What does it affect?

• Features?

• Epidemiology?

• Diagnosis?

• What is it?

  • Progressive Neurodegenerative disorder

• What does it affect?

  • Injury + cell death of lower (Brain stem, SC) /upper motor neurons (motor cortex)

• Features:

  • No sensory loss or sphincter disturbance

  • Cognitive dysfunction (5-20% with frontotemporal dementia) 

  • Parkinsonism

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Epidemiology:

• Incidence: 2 per 100,000

• Prevalence: 6 to 8 per 100,000

• Primarily affects middle-aged to elderly individuals, men slightly more

• Most are sporadic; only 5-10% is inherited (autosomal dominant)

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Diagnosis

• Clinical features of UMN and LMN dysfunction

• Electrodiagnostic study evidence (EMG/NCS) of UNN and LMN dysfunction in multiple areas

• Exclusion of other diagnoses, such as:

  • Other motor neuron diseases:

    • Primary lateral sclerosis, Spinal muscle atrophy

  • Spinal cord disorders:

    • Multilevel spinal cord and root compression (disc, osteophytes, tumor)

    • Combined cervical myelopathy and peripheral neuropathy

    • Radiation myelopathy

  • Myopathies:

    • Inclusion body myositis, Sjogren syndrome, thyrotoxicosis

1. Describe the treatment Components of ALS

2. Describe how we treat the symptoms

Treatment components:

• Patient education

• Disease-directed

• Adaptive/supportive care

  • Dysphagia

    • Percutaneous gastrostomy

• Respiratory support

  • Non-invasive ventilation

• Functional dependence

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Symptomatic

• Limb spasticity

  • muscle relaxants

• Excessive salivation

  • anticholinergics, sympathomimetics, botulinum toxin

• Pseudobulbar Palsy

  • neudexta

• Pain 

  • Standard medication

• Fatigue

  • Standard medication

• Depression

  • Standard medication

Describe Riluzole

• AKA

• MOA

• Dif. Forms

Riluzole

• AKA:

  • [Rilutek]

• MOA:

  • Glutamate pathway antagonist

• Different Forms:

  • thickened liquid form [Tiglutik]

  • oral film [Exservanl

NOTE: Slightly extends survival

Describe Edaravone 

• AKA

• MOA

• Purpose

• Forms

Edaravone 

• AKA: [Radicava]

• MOA:

  • Free radical scavenger

• Purpose:

  • Slows decline in physical function

• Forms:

  • Oral formulation approved in 2022

Describe Qalsody 

• AKA?

• MOA?

Qalsody 

• AKA: [tofersen]

• MOA:

  • treat ALS associated with a mutation in the superoxide dismutase I [SODI] gene.

Describe Relyvrio 

• AKA

• MOA

Relyvrio 

• AKA:

  • [AMX0035]

• MOA:

  • Combo of phenylbutyrate and tarursodiol -> prevent nerve cell death by blocking stress signals

Describe Peripheral Neuropathy

• Definition

• Structures affected

Peripheral Neuropathy (PN)

• Definition:

  • Disorder affecting any part of the peripheral nervous system

• Structures affected 

  • Spinal and cranial nerves

    • except olfactory (I) and ophthalmic (II)

  • Ventral and dorsal nerve roots

  • Sensory and motor terminals

  • Part of the autonomic nervous system

Describe Radiculopathy

• Features

• Examples

Radiculopathy

• Features:

  • Pain, sensory, motor, and reflex change(s) solely in distribution of the nerve root(s)

• Examples

  • Cervical radiculopathy

  • Lumbar radiculopathy

Describe Plexopathy

• Features

• Examples

Plexopathy

• Features:

  • Only one limb is affected

  • Motor, sensory, and reflex loss does not conform to a pattern of several adjacent nerve roots or nerves

• Examples

  • Brachial plexus neuropathy

  • Cervical rib/thoracic outlet syndrome

  • Lumbosacral plexus neuropathy

Describe Mononeuritis Multiplex

• Features

• Causes?

• Features

  • Acute or subacute evolution

  • Multiple nerve involvement with complete/almost complete sensorimotor paralysis in distribution of individual peripheral nerves

• Causes

  • Diabetes

  • Vasculitis

  • Sarcoid

  • Leprosy

  • (AIDS)

Describe Polyneuropathy

• Features

• Causes

• Less Common Causes

Features

• Weakness is relatively symmetrical from the beginning and progresses bilaterally

• Reflexes are lost in affected parts but particularly @ ankles

• Sensory complaints/loss of sensation are most pronounced distally

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Causes

• Diabetes

• Other metabolic disease

  • Uremia 

  • Neuropathy with celiac disease

  • Thyroid disease

  • Vitamin deficiencies (B12)

• Inflammatory

  • Guillain-Barre

  • Chronic inflammatory demyelinating polyneuropathy (CIDP)

  • Others

• Alcoholism

• Toxic

  • Chemotherapy

    • Platinum, Vinca alkaloids

  • Medications

    • Amiodarone

    • Isoniazid

    • Others: Colchicine, Hydralazine, Metronidazole, Nitrofurantoin

• Immune disorders

  • Vasculitis, systemic lupus erythematosus (SLE), rheumatoid arthritis, etc.

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Less Common Causes:

• Hereditary (Charcot-Marie-Tooth)

• Monoclonal gammopathy

• Cancer/hematologic malignancies

• Infections

  • HIV polyneuropathy

  • Lyme disease

  • Hepatitis C

How to evaluate for pt with Peripheral Neuropathy

Evaluation of the Patient with Peripheral Neuropathy

• History and Physical Exam

• Recommended initial laboratory tests

  • Biochemical testing

    • Fasting blood sugar/A1C

    • Renal function

    • Liver profile

    • B12

    • Protein electrophoresis/immunofixation

  • Hematologic

    • CBC

    • ESR

• Others

  • Tests for infectious agents as indicated

  • CSF examination

  • Electrodiagnostic tests in selected cases

Differentiate between NCS and EMG

What information does the EMG/NCS provide?

What information does the EMG/NCS provide?

• Location of pathology

  • Anterior horn cell, nerve root, nerve, neuromuscular junction, or muscle

• Peripheral nerve involvement type

  • Axonal, Demyelinating, Mixed

• Severity of involvement

• Estimates chronicity

Describe Diabetic Neuropathy: Distal Sensorimotor Polyneuropathy (DSP)

• STATs

• Presentation

• Medical History

• Neurologic Exam

• Course

• When should I screen?

Diabetic Neuropathy: Distal Sensorimotor Polyneuropathy (DSP)

• STATs

  • Most common neuropathy in diabetes

• Presentation

  • Pain, paresthesias, or dysesthesias of feet

  • Complications: Foot ulcers, muscle and joint disease (claw toe, Charcot arthropathy)

  • May be asymptomatic

• Medical History

  • Associated with diabetic nephropathy and retinopathy

• Neurologic Exam

  • Impaired of pain, light touch, and temperature sensations

  • Loss of vibratory sensation, altered proprioception

  • Decreased or absent ankle reflexes

• Course

  • Incidence of diabetic neuropathy increases over time

• When should I screen?

  • 5 years after diagnosis of type 1 DM

  • At the time of diagnosis of type 2 DM

NOTE: Early detection followed by therapeutic interventions can reduce complications

List the DSP Complications

Describe the diagnosis and treatment of Diabetic Neuropathy

Diagnosis

• Clinical

  • Neuropathic symptoms, 

  • Distal sensory loss, +/- decreased or absent ankle reflexes

• nerve conduction studies

  • Only when atypical

    • (Rapid progression, more weakness than sensory loss, asymmetric, more proximal)

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Treatment

• Optimize control of diabetes

• Symptomatic

  • Tricyclic antidepressants, SSRI/SNRI, anti-epileptic drugs, capsaicin, analgesics

Describe Guillain-Barre Syndrome (GBS)

• What is it?

• Associated w/?

• Clinical Features?

• Course

Guillain-Barre Syndrome

• What is it?

  • Acute monophasic paralyzing illness

    • usually provoked by a preceding infection

• Associated with:

  • Immunizations

  • Infections

    • Respiratory tract infection, Epstein Barr virus, Campylobacter jejuni, Covid-19

  • Can be sporadic

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Clinical features:

• Acute motor weakness

  • Ascending paralysis

  • facial, oropharyngeal, and oculomotor muscles

  • 30% develop respiratory muscle weakness with need for ventilatory support

• Sensory Symptoms (less prominent)

  • Paresthesia

  • Radicular pain

• Autonomic symptoms

  • Tachycardia

  • Hypo/Hyper tension

  • Loss of sphincter control, urinary retention

  • Flushing, sweating

  • Ileus

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Course

• Symptoms progress over 2-4 weeks

• Brief period of stabilization

• Recovery is slow and can take weeks to months

• Most recover with no or little sequelae

Describe the treatment of GBS

• Management

• Supportive care

• Immunization

Management

• Hospitalize patient due to risk of respiratory compromise

• Directed vs. immune system

  • Intravenous immunoglobulin (IVIG)

  • Plasma exchange

  • Note: Steroids are NOT effective

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Supportive care:

• Manage cardiovascular complications

• Bowel and bladder care

• Rehabilitation

• Pain management

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Immunization:

• Avoid revaccinating with immunization associated with GBS

  • Usually influenza

  • Warning with J&J Covid-19 vaccination

• May give other immunizations

• Do not give immunizations till a year after the GBS episode

Describe Bell’s Palsy

• What is it?

• Clinical Features

• DDX

• Treatment

Bell’s Palsy

• What is it?

  • Sudden idiopathic facial paresis of [LMN] type

• Clinical features

  • LMN facial palsy involving ENTIRE half of face

  • Hyperacusis or impaired taste may occur

  • No other neurologic abnormalities

• DDX

  • Herpes simplex virus

  • Herpes-varicella-zoster

  • Lyme disease

  • Connective tissue disease

  • Others

• Treatment

  • Anti-viral/Corticosteroids if < 3 days

  • Protect the eye if unable to close

  • CN V and VII transfer

Describe Carpal tunnel syndrome

• What is it

• Presentation

• Seen With

• Treatment?

• What is it?

  • Compression of the median nerve between the carpal ligament and other structures within the carpal tunnel

• Presentation

  • Pain, burning, and tingling in the distribution of the median nerve

  • Late weakness or atrophy of the thenar eminence

• Seen with:

  • Repetitive wrist activities/trauma

  • Systemic diseases (diabetes, mellitus, rheumatoid arthritis)

  • Pregnancy (fluid retention)

• Treatment

  • Splinting, steroid injection

  • Surgery when severe, protracted