SPINAL CORD, MOTOR NEURON, PERIPHERAL AND NEUROMUSCULAR DISEASE

What type of disorder is Spinal Muscular Atrophy?

Lower motor neuron disorder

What cells degenerate in Spinal Muscular Atrophy?

Anterior horn cells in the spinal cord and bulbar motor nuclei

Which chromosome is the most common form of Spinal Muscular Atrophy linked to?

Chromosome 5q13

What is spinal muscular atrophy the most common cause of?

infantile death

What is spinal muscular atrophy the second most common of?

neuromuscular disease (second to Duchenne's muscular dystrophy)

What are the clinical features of spinal muscular atrophy related to muscle strength?

Symmetric muscle weakness and atrophy of limbs

What type of involvement can occur in spinal muscular atrophy?

Variable bulbar involvement

What is a common symptom of spinal muscular atrophy that involves involuntary movements?

Tremor

What type of pathological evidence is associated with spinal muscular atrophy?

Pathologic evidence of motor denervation

What is a key feature of spinal muscular atrophy related to muscle weakness?

Symmetrical muscle weakness, proximal greater than distal.

What muscle involvement is observed in severe cases of spinal muscular atrophy?

Trunk muscles involved, with poor head and trunk control.

What type of weakness is present in spinal muscular atrophy, specifically regarding intercostal muscles?

Intercostal weakness, but sparing of the diaphragm.

What are the clinical signs of denervation in spinal muscular atrophy?

Fasciculations or tremor.

What laboratory tests can provide evidence of denervation in spinal muscular atrophy?

EMG or muscle biopsy.

What is a clinical exclusion criterion for spinal muscular atrophy related to the central nervous system?

CNS dysfunction

What is a clinical exclusion criterion for spinal muscular atrophy that involves joint deformities?

Arthrogryposis

What is a clinical exclusion criterion for spinal muscular atrophy that involves issues with other organ systems?

Abnormalities of other organ systems

What is a clinical exclusion criterion for spinal muscular atrophy related to the sense of touch?

Sensory loss

What is a clinical exclusion criterion for spinal muscular atrophy involving muscle weakness in the face or eyes?

Severe facial or extraocular muscle weakness

What is a clinical exclusion criterion for spinal muscular atrophy that indicates increased muscle tone or reflexes?

Hypertonia or hyperreflexia

What is one laboratory exclusion criterion for spinal muscular atrophy?

High creatine kinase

What is another laboratory exclusion criterion for spinal muscular atrophy?

Aminoaciduria

What is a laboratory exclusion criterion for spinal muscular atrophy related to organic compounds?

Organic aciduria

What enzyme deficiency is a laboratory exclusion criterion for spinal muscular atrophy?

Hexosaminidase A or B deficiency

What condition related to blood proteins is a laboratory exclusion criterion for spinal muscular atrophy?

Monoclonal gammopathy

What type of biopsy evidence is a laboratory exclusion criterion for spinal muscular atrophy?

Biopsy evidence of lipid or glycogen storage disease or mitochondrial abnormality

What nerve conduction characteristic is a laboratory exclusion criterion for spinal muscular atrophy?

Abnormally slow nerve conduction velocity

spinal muscular atrophy type 0

- arthogryposis

- prenatal onset

- never breathe independently

- die at 0-6 months

spinal muscular atrophy type I

- acute

- onset at birth-6 months

- never sit

- die at <2 years

spinal muscular atrophy type II

- intermediate

- onset at <18 months

- never stand

- die at >2 years

spinal muscular atrophy type III

- mild

- onset at >18 months

- die as adults

spinal muscular atrophy type IV

- adult

- onset at >18 months to adulthood

- die as adults

What does the term 'diabetic neuropathy' refer to?

A disorder of the peripheral nervous system derived from diabetes mellitus

What conditions can diabetic neuropathy progress independently of?

Hypertension, hyperlipidemia, smoking, alcohol abuse, and peripheral vascular disease

What is the most common type of diabetic neuropathy?

Generalized sensorimotor polyneuropathy (75%)

With which conditions does generalized sensorimotor polyneuropathy correlate?

Retinopathy and nephropathy

Do all diabetics have neuropathy as a cause of neuro symptoms?

No, not all diabetics have neuropathy as the cause of neuro symptoms and vice versa.

Generalized sensorimotor polyneuropathy frequently presents with symptoms of...?

Occult/undiagnosed diabetes mellitus (DM)

What are common symptoms in the distal lower limbs for generalized sensorimotor polyneuropathy?

Paresthesias (pins-and-needles or tingling) and pain (dull, stabbing, or burning)

How does the symptom progression occur in generalized sensorimotor polyneuropathy?

Progresses distal-to-proximal

What is the initial presentation of symptoms in generalized sensorimotor polyneuropathy?

Begins asymmetrical and becomes bilateral and symmetrical with time

Is there motor involvement in generalized sensorimotor polyneuropathy?

Rarely motor involvement, occasional (advanced) autonomic involvement

How is generalized sensorimotor polyneuropathy diagnosed?

Diagnosis of exclusion by screening for various conditions

What conditions are screened for in the diagnosis of generalized sensorimotor polyneuropathy?

Uremia, alcoholic/nutritional issues, connective tissue disorders, vasculitis, B12 deficiency, hypothyroidism, toxic, paraneoplastic, paraproteinemia, amyloidosis, hereditary

Management of Generalized sensorimotor polyneuropathy

aggressive glycemic control, and if with important pain, use of Gabapentin or tricyclic antidepressants

What are some connective tissue neuropathies?

- vasculitic neuropathy

- distal symmetrical axonal neuropathy

- trigeminal sensory neuropathy

Vasculitic Neuropathy Pathogenesis/definition

Inflammatory occlusion of blood vessels produces ischemic infarction of one or more nerves

What is a common initial symptom of vasculitic neuropathy?

Acute pain that develops to a burning sensation.

What are some secondary symptoms associated with vasculitic neuropathy?

Loss of pain and temperature sensation, weakness

Which nerve is commonly affected in the lower limb by vasculitic neuropathy?

Peroneal nerve.

Which nerve is commonly affected in the arm by vasculitic neuropathy?

Ulnar nerve.

What is a common motor symptom of vasculitic neuropathy?

Weakness.

Vasculitic neuropathy EMG

reduced recruitment of motor unit potentials, fibrillation of action potentials, decreased amplitude of sensory nerve with normal conduction velocities

What is a suspected underlying connective tissue disorder of vasculitic neuropathy that is usually not previously diagnosed?

Polyarteritis nodosa

What is a suspected underlying connective tissue disorder of vasculitic neuropathy that is usually an established diagnosis?

Rheumatoid arthritis

What are three other suspected underlying connective tissue disorders of vasculitic neuropathy?

- Systemic Lupus erythematosus

- Sjogren's syndrome

- Wegener's granulomatosis

What is the first-line treatment for vasculitic neuropathy?

Glucocorticoids (oral prednisone or IV methylprednisolone)

How long should treatment last for vasculitic neuropathy associated with Polyarteritis nodosa or rheumatoid vasculitis?

4-12 months

What additional medication is added for systemic and necrotizing vasculitis in the treatment of vasculitic neuropathy?

Cyclophosphamide

How long should cyclophosphamide be used in the treatment of vasculitic neuropathy with systemic and necrotizing vasculitis?

1 or more years

Vasculitic neuropathy recovery

likely 30% at 3 months, 60% at 6 months and 86% at 1 year

What sensory symptoms are associated with Distal symmetrical Axonal Polyneuropathy?

• Diminished awareness of pain, temperature, touch, position

• "Feeling of walking on sand or marbles"

• Non-specific pain when there are "paresthesias"

What is a key differentiating factor of Distal symmetrical Axonal Polyneuropathy?

Length dependency of affected nerve fibers leads to symmetrical symptoms with respect to time of onset.

In Distal symmetrical Axonal Polyneuropathy, which limbs must be symptomatic first?

Lower limbs must be symptomatic before any symptom on fingers of hands.

What is a key aspect of managing Distal symmetrical Axonal polyneuropathy?

Symptomatic pain management

What rehabilitative devices can be used for ankle weakness in Distal symmetrical Axonal polyneuropathy?

Orthotic shoe inserts or ankle-foot orthoses

What is Trigeminal Sensory Neuropathy?

• Early manifestation of Systemic Sclerosis or

• Manifestation of know disease (Sjogren, SLE, RA)

What is a clinical symptom of Trigeminal Sensory Neuropathy?

Small patch of numbness around the mouth or cheek, slowly progressing unilaterally.

What sensations are associated with Trigeminal Sensory Neuropathy?

Paresthesia and/or pain.

What reflex is absent or blunted in Trigeminal Sensory Neuropathy?

Corneal reflex.

What is a key aspect of managing Trigeminal Sensory Neuropathy?

Addressing underlying connective tissue disease.

What percentage of patients with Trigeminal Sensory Neuropathy respond to prednisone?

Less than 10%.

Is prednisone typically used in the management of Trigeminal Sensory Neuropathy?

Not typically used unless warranted by the underlying condition.

What are some toxic peripheral neuropathies?

- Organophosphate (OP)

- Hexacarbons

- Acrylamide

- Vacor

- Trichlorethylene

- Ethylene oxide

- Polychlorinated biphenyls (PCBs)

- Lead

What are some common uses of organophosphates (OP)?

Insecticides, plastic modifier, flame retardants, lubricants, petroleum additives.

What enzyme is irreversibly inhibited by organophosphates?

Acetyl cholinesterase (AChE)

What increases the incidence of organophosphate exposure?

Participation in agricultural (field or industry) activities.

Acute/type I Organophosphate (OP)

<24hr onset

Intermediate/type II Organophosphate (OP)

12-96 hr onset (after recovery from acute) = muscle weakness

Organophosphate-induced delayed polyneuropathy (OPIDP):

1-3 week onset = chronic low level exposure = painful paresthesias of feet with cramps in calves and prominent weakness

Organophosphate (OP) Symptoms

• Nausea, vomiting, diarrhea, salivation, sweating, micturition and tachycardia

• From decreased alertness to convulsions/coma

Organophosphate (OP) Management

• Removal of exposure, education of preventive measures

• Symptomatic as required (from atropine to intubation)

• Pralidoxime accelerates reactivation of AChE.

Hexacarbons Background

Present in solvents, glues, lacquers = dermal or inhalation exposure

Acute Hexacarbons

narcosis and CNS depression that resolves without sequelae

Chronic Hexacarbons

recreational "glue sniffing" = peripheral nerve damage and neuropathy (motor involving cranial nerves)

Hexacarbons symptoms

Weakness of 4 extremities initially with autonomic dysfunction, severe cases with abdominal pain, malaise, leg cramps

What syndrome is associated with toxic exposure to organophosphates and acrylamide and is a differential diagnosis of hexacarbons?

Gillain-Barre syndrome

What toxic metabolite can be identified in urine samples related to hexacarbons?

2,5-Hexanedione

What electrophysiologic change is observed in distal motor conduction velocities due to hexacarbons?

Slowing of distal motor conduction velocities

Hexacarbons management

No specific management, most important prevention measures, recovery adequate except when with neuropathy/nerve damage

Acrylamide Background

chemical used in grouting, as a flocculator in wastewater. The metabolite is glycinamide and is neurotoxic

Acrylamide symptoms

Anorexia, headache, malaise and dizziness

What are the neurological symptoms associated with high level exposure to Acrylamide?

Encephalopathy with seizures and truncal ataxia

What autonomic dysfunction symptoms can occur due to high level exposure to Acrylamide?

Excessive sweating and blood pressure fluctuations

What vasomotor changes can occur due to high level exposure to Acrylamide?

Vasomotor changes in fingers and toes

Chronic low level exposure to Acrylamide

neuropathy and dermatitis

Acrylamide Workup

Clinical and electrophysiologic: described symptoms and reduced sensory potential amplitudes with normal motor conduction velocities and amplitudes

Acrylamide Management

Preventive, removal of exposure. Low degree of sequelae in mild cases

Vacor Background

Chemical used in rodenticides, structurally related to nicotinamide

What type of axonopathy is associated with Vacor classification?

Acute distal axonopathy with autonomic involvement