Disorders of the Peripheral N. Flashcards by Rai Christiana

Disease or injury of the peripheral, sensory, motor or autonomic nerves

Neuropathy

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Damage to a single peripheral nerve

Mononeuropathy

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Damage to ≥ 2 peripheral nerves
Results in asymmetrical distribution

Mononeuritis multiplex

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Damage to terminal branches of multiple nerves
Results in symmetrical, distal distribution

Polyneuropathy

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Damage to a nerve plexus, eg.. brachial plexus

Plexopathy

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Damage to nerve root
Distribution follows corresponding dermatome

Radiculopathy

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selective injury to cell body of axon

Neuronopathy

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nerve roots

Radiculopathy

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Neuropathy

Rate of onset

• Acute - <4 weeks
• Subacute
• Chronic - > 12 weeks

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Neuropathy

Type of peripheral nerve affected:

• Pure motor
• Pure sensory
• Autonomic
• Mixed sensorimotor

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Neuropathy Distribution

symmetrical or asymmetrical, distal or proximal or multifocal; generalized

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Four Categories of Nerve Injury

Neuronal degeneration
Wallerian degeneration
Axonal degeneration
Segmental demyelination

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Damage to the nerve cell bodies with subsequent degeneration of their contiguous axons

• Neuronopathy
• Sensory neuronopathy / ganglionopathy
• Motor neuronopathy
• Autonomic neuronopathy

Neuronal degeneration

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• Damage to axon at a specific point below the cell body, with degeneration distal to the injury

Wallerian degeneration

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• Degeneration of the myelin and axis cylinder distal to the site of axonal interruption with central chromatolysis secondary to axonal disease

Wallerian degeneration

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Dying forward

Wallerian degeneration

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Dying back

Axonal Degeneration

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• Diffuse axonal damage
• Degeneration of myelin and axis cylinder from distal to proximal segments secondary to a neuronal disease or mechanical nerve compression

Axonal degeneration

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• Axons undergoes earliest and most severe changes with diffuse neuronal injury
• Hands and feet followed by gradual proximal ascent with continued injury

Axonal degeneration

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Injury to myelin sheath without injury to the axon

Segmental demyelination

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Symptoms of Peripheral Neuropathy

• Weakness
• Loss of DTRs
• Loss of sensation (negative symptoms)
• Paresthesias, dysesthesias, pain (positive symptoms)
• Sensory ataxia
• Anatomic changes
• Autonomic dysfunction
• Fasciculation, cramps and spasms

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Large Fiber Neuropathy manifestation

• Loss of joint position and vibration sense
• Sensory ataxia
• Dull, deep, toothache like pain, painful cramps and fasciculations, muscle atrophy, weakness
• Decreased DTRs
• EMG - abnormal

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Small Fiber Neuropathy manifestation

• Loss of pain and temperature
• Autonomic dysfunction
• GI - abdominal discomfort, constipation, diarrhea
• CV - orthostatic hypotension, arrhythmias, syncope
• Bladder - weak urinary stream, straining to void, incomplete emptying
• Skin - heat intolerance, decreased sweating, discoloration
• Burning, hypersensitivity, allodynia, prickling shooting pain
• Numbness, tightness, coldness
• Normal reflexes
• EMG - normal

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Diagnosis of Peripheral Neuropathy

• NCS-EMG
• Axonal vs demyelinating
• Motor vs sensory or both
• Large fiber vs small fiber

• Sural nerve biopsy
• Skin biopsy for small fiber neuropathy

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Length dependent (stocking and glove or distal symmetric); multifocal (vasculitic)

Axonal

Length-dependent loss (ankle reflexes lost initially)

Axonal

Depending on type of fibers involved - pain, temperature, light touch, vibration; length-dependent distribution

Axonal

Weakness Distal, symmetric

Axonal

Autonomic Yes, with small fiber loss (diabetes, amyloidosis)

Axonal

Electrophysio Normal or mild slowing (not out of proportion to axonal loss) No

Axonal

Normal csf

Axonal

Acute - ischemia; high dose toxin; critical illness Subacute - toxic; nutritional; paraneoplastic Chronic - metabolic; hereditary

Axonal

Occasional; especially toxic in which dorsal columns affected

Axonal

Slow recovery

Axonal

Axon regrowth guided by schwann cell and basal lamina tubes

Axonal

Usually diffuse (proximal and distal) or patchy (multifocal); occasionally length dependent

Demye

Usually diffusely reduced or absent; can be patchy or length dependent

Demye

Usually mild. Prominent proprioception and vibration loss. May have sensory ataxia; pain and temperature sense not lost alone

Demye

Weakness Diffuse; can mimic length-dependent process

Demye

Ai Only in Guillain-Barré or autoimmune dysautonomia

Demye

Electrophysio Marked slowing (< 80% of lower limit of normal) Yes, with acquired demyelination

Demye

Elevated csf

Demye

Acute - Guillain-Barré Subacute -chronic inflammatory demyelinating polyneuropathy (CIDP); monoclonal gammopathy Chronic - hereditary; CIDP; monoclonal gammopathy

Demye

Cns Rare; hereditary metabolic disorders (leukodystrophy)

Demye

Rapid recovery

Demye

Schwann cell proliferation and remyelination with shortened internodes

Demye

Guillain-Barre syndrome

Diabetes Amyloidosis

CIPD

Uremia Diabetes

Multifocal motor

Alcohol Guillain-Barré syndrome

Charcot Marie disease

HIV Porphyria

Myeloma

Paraneoplastic Hereditary sensory neuropathy

Diabetes

Sjögren syndrome

Diptheria

Connective tissue diseases Toxins/medications Vitamin B12 deficiency

Most common mononeuropathy

Nerve entrapment, carpal tunnel syndrome

Mononeuropathy Commonly affected n.

• Medial nerve • Ulnar nerve • Peroneal nerve

Common causes of mononeuropathy

• Compressive • Ischemia • Trauma • Demyelination

acute motor axonal neuropathy

Anti-GM1 IgG Ab

multifocal motor neuropathy

Anti-GM1 IgM Ab

Miller fisher variant of GBS

Anti-GQ1b Ab

carcinomatous paraneoplastic sensory neuronopathy

Anti-Hu Ab

distal predominantly sensory ataxic neuropathy

Anti-myelin associated glycoprotein (MAG) Ab -

Symmetric polyneuropathy with prominent distal sensory loss

Anti sulfatide antibody

Idiopathic acute unilateral facial paralysis • Unknown infectious agent - ?viral • 1 in 5,000 people Inability to wrinkle brow - Drooping eyelid; inability to close eye Inability to puff cheek; asymmetrical smile Drooping corner of mouth; dry mouth

Bell's Palsy

Unilateral facial weakness, facial droop Hyperacusis or hearing loss Corneal dryness due to incomplete eye closure Loss of taste in anterior 2/3 of tongue Impaired lacrimation and salivation

Bell’s palsy

Cn vii

Mixed motor and sensory • Parasympathetic

Cn vii motor sve

muscles of face (facial expression) and scalp, stapedius muscle, posterior belly of digastric, stylohyoid muscles

Cn vii sensory sva

- taste from anterior 2/3 of tongue from floor of mouth and palate

Cn vii sensory gsa

sensation from a small region near the external auditory meatus

Cn vii parasympathetic gve

secretomotor to submandibular and sublingual glands, lacrimal glands and glands of nose and palate

Bell’s palsy treatment

• Pharmacotherapy • Corticosteroids - probably effective in improving functional outcome • 1mg/kg/day x 1 week • Antiviral - acyclovir or valacyclovir • Supportive therapy • Eye protection • Artificial tears • Rehabilitation

Bell’s palsy prognosis

• 70-90% improve with or without treatment • 10% have recurrence ipsilaterally or contralaterally

• Separate involvement of more than one peripheral (less often cranial) nerve by a single disease • Sensory disturbance and weakness in the distribution of 2 or more affected peripheral nerves • Autoimmune attack on vasculature of the peripheral nerve resulting in inflammation, occlusion and ischemia in different peripheral nerves through out the body • Usually secondary to generalized vasculitis or vasculopathy • May also affect respiratory nerves

Mononeuropathy multiplex

Mononeuropathy multiplex tx

IVIg or corticosteroids

Immune-mediated disorder that targets peripheral nerves • Incidence: 1-2/100,000

Guillain Barre Syndrome (GBS)

Gbs type

1. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) 2. Miller Fisher syndrome (MFS) 3. Acute motor axonal neuropathy (AMAN) 4. Acute motor-sensory axonal neuropathy (AMSAN) 5. MFS-GBS overlap syndrome

Main features of Guillain Barre Syndrome (GBS)

• Rapidly progressive, ascending paralysis • Areflexia • Increased CSF protein • Demyelination on NCS • Can progress to respiratory compromise

Gbs most common

Acute inflammatory demyelinating polyneuropathy (AIDP)

Ascending paralysis Minor sensory symptoms Antibodies Nonspecific EMG/NCS Findings Demyelination on NCS Absent F waves

Acute inflammatory demyelinating polyneuropathy (AIDP)

Flaccid paralysis Often with Campylobacter jejuni infection IgG anti-GM IgG anti-GD Reduced motor amplitudes Normal sensory studies

Acute motor axonal neuropathy (AMAN)

Acute (<1 wk) Profound quadriparesis Ventilation often required IgG anti-GM, Reduced or absent motor amplitudes Reduced or absent sensory amplitudes Axonal injury by EMG

Acute motor sensory axonal neuropathy (AMSAN)

Ataxia Areflexia Ophthalmoplegia IgG anti-GQ Decreased sensory nerve action potential Motor conductions often normal

Miller Fisher syndrome

Ophthalmoplegia or ataxia, followed by limb weakness IgG anti-GQ Decreased sensory nerve action potential Reduced motor amplitudes

Miller Fisher-Guillain Barré (MFS-GBS) overlap syndrome

• 85-90% of GBS cases • Progressive symmetric weakness of extremities with loss of reflexes • Demyelination starts at the proximal nerves then progresses • Preceded by infection (nonspecific respiratory or Gl infection) • Begins after 1-3 weeks • Reaches nadir by 2 weeks in 50% • If disease progresses for more than 4 weeks = CIDP • Can involve cranial and autonomic nerves • ¼ - life threatening respiratory paralysis, arrhythmias and BP fluctuations

Acute inflammatory demyelinating polyneuropathy (AIDP)

Gbs tx and dx

Diagnosis • CSF studies - increased protein, normal to mild lymphocytic pleocytosis • NCS-EMG - demyelination with reduced motor conduction velocities and prolonged distal motor latencies within 3-5 days of symptoms onset, absent F wave responses; reduced recruitment, evidence of axonal injury • Treatment • IVig (0.4g/kg/day for 5 days) • Plasmapheresis

Gbs prognosis

• Disease progression plateaus after 2-4 weeks, followed by gradual recovery • 20-25% require mechanical ventilation • 5% die from complications of respiratory failure or autonomic dysfunction • 25% have residual motor weakness after 1 year • Poor prognostic factors for walking independently at 6 mos: • Older age • Diarrhea • More severe weakness and rapid progression • Low CMAP amplitudes

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) main features

• Gradual, progressive weakness over at least 2 months • Areflexia • Increased CSF protein without increased cell count • Evidence of demyelination on NCS

• Older than 50 yo • Disproportionately affects men • Stepwise progression with periods of plateau or steady declining course or recurrent episodes • Most have initially predominantly motor symptoms but examination reveals both motor and sensory dysfunction • Symmetric proximal and distal weakness • 50% atypical presentation with focal weakness then becomes multifocal or bilateral

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

CIPD Dx

NCS - demyelination with slowed CVs, prolonged distal motor latencies, conduction block, abnormal temporal dispersion and abnormal late responses • CSF analysis - elevated protein, normal or mild lymphocytic pleocytosis

Multifocal Motor Neuropathy (MMN) • Main features:

• Asymmetric distal weakness, especially of the hands • Subacute to chronic progression • Proximal conduction block in motor nerves • Elevated anti-GM1 Ab

• Chronic, immune-mediated motor neuropathy • Age of onset: 20-75 years • Most common: Male in 50-60s • Asymmetric, slowly progressive weakness usually beginning in the hands • Atrophy and fasciculations may be present • Normal or absent reflexes • Cranial nerve involvement rare

Multifocal Motor Neuropathy

Multifocal Motor Neuropathy Dx and Tx

NCS-EMG - focal demyelination and conduction blocks in proximal motor scarents • Increased anti-GM1 IgM • Treatment: • IVig (2g/kg in divided doses over 5 days followed by maintenance doses) ・ Cyclophosphamide

Leprosy main ft

• Sensory or sensorimotor polyneuropathy • Ulnar and tibial nerves disproportionately affected • Tendon reflexes preserved • Cutaneous manifestations

Leprosy aka

Hansen’s disease

Leprosy bacteria

Mycobacterium leprae

Leprosy transmission

Respiratory and prolonged skin contact

14-20% have neuropathy • Infected monocytes from broken skin and mucosal membranes carry M leprae into the nerves during normal transport • Bacteria then attacks Schwann cells, producing axonal damage by infiltrating inflammatory cells and granuloma formation

Leprosy

Leprosy types

Tuberculosis Borderline Lepromatous

• Patient is not immunocompromised • Good cell mediated immunity • Lesions are usually small and solitary • Large nerve trunks • Mononeuritis or mononeuritis multiplex • Cured by multiple drug therapy

Tuberculoid

• Unstable form • Dimorphic punched out lesions

Borderline

• Multiple lesions maculopapular and nodular • Diffuse infiltrated skin with madarosis and leonine facies • Bacilli proliferates within Schwann cells and macrophages in the endoneurium and perineurium especially in cool areas of the body (ears, dorsum of hands, forearms and feet) • Low resistance (immunocompromised)

Lepromatous

Leprosy 3 cardinal sign

1. Definite loss of sensation in a pale (hypopigmented) or reddish skin patch 2. Thickened or enlarged peripheral nerve with loss of sensation and/or weakness 3. Microscopic detection of bacilli

Leprosy Dx and Tx

• Diagnosis • NCS-EMG • Skin punch biopsy • Treatment • Rifampin • Clofaximine • Dapsone

Diphtheritic Polyneuropathy Main ft

• Localized febrile pharyngitis initially • Diphtheritic membrane, which may cover posterior pharynx • Purely demyelinating sensorimotor neuropathy

Diphtheritic Polyneuropathy bacteria

Corynebacterium diphtheriae

Corynebacterium diphtheriae • Emits exotoxin that cause cardiomyopathy and segmental demyelination of nerve roots or peripheral nerves • Mortality rate: 10% • Direct obstruction of airway or neuropathic weakness of respiratory muscles • Young children and older patients

Diphtheritic Polyneuropathy

Diphtheritic Polyneuropathy Dx and Tx

Diagnosis: • Culture from pharynx • NCS - severe demyelinating neuropathy • CSF analysis - elevated protein • Treatment: • Antibiotics - penicillin, erythromycin • Prevention - vaccination

Alcohol neuropathy main ft

• Gradual-onset, distal, symmetric sensory loss with pain • Weakness is a late complication • Begins after months to years of alcohol abuse • Diminished reflexes

• Direct alcohol toxicity and thiamine (B1) deficiency • Axonal problem • Treatment: abstinence and thiamine supplementation • Recovery rarely complete

Alcoholic Neuropathy

Vitamin B6 (Pyridoxine) Deficiency main ft

• Associated with isoniazid, hydralazine and penicillamine therapy • Preventable with supplementation • Slowly progressive distal sensory and motor deficits

most common cause of neuropathy worldwide

Most common diabetic neuropathy

Distal symmetric sensorimotor neuropathy

Numbness, paresthesias, dysesthesias, hyperesthesias, ataxia Any of the above plus distal weakness

Distal Symmetric Neuropathy Large-fiber sensory neuropathy Sensorimotor neuropathy

Numbness, paresthesias, painful dysesthesias, hyperesthesias Subacute, severe neuropathic pain and rapid weight loss Erectile dysfunction, orthostasis, cardiac dysrhythmia, diarrhea, constipation

Small-Fiber Neuropathy "Pure" small-fiber neuropathy Diabetic neuropathic cachexia Autonomic neuropathy

Diplopia, pupil-sparing third nerve palsy, hemifacial weakness Pain, followed by numbness or weakness in a radicular distribution Pain, followed by numbness, weakness, or both in territory of a single nerve

Ischemic Mononeuropathy Cranial (eg, CNs III, VI, VII) Radicular (thoracic, lumbosacral) Peripheral (eg, femoral)

Subacute weakness and atrophy of proximal leg muscles Subacute weakness, numbness, and atrophy in thorax and abdomen

Regional Neuropathic Syndromes Diabetic amyotrophy Diabetic thoracoabdominal neuropathy

Diabetic neuropathy pathophysio

• Oxidative stress damage, accumulation of sorbitol, advanced glycosylation end products, and disturbance of hexosamine, protein kinase C and polymerase pathways • Neurovascular impairment with poor reparative processes • Endothelial dysfunction

• Starts with numbness, paresthesia or dysesthesias in feet • Ascend up the leg • Eventually affect upper extremity • Loss of protective foot sensation • Increase chances of cutaneous ulcerations, impaired healing

Distal symmetric neuropathy

• Damaged C fibers • Loss of distal pinprick and temperature sensation • Development of burning, electric, aching, stabbing, pins and needles dysesthesia and pain • Allodynia

• Small fiber and painful neuropathy

• 50% of patients • CV - limited activity tolerance, tachycardia, postural hypotension, myocardial infarction • Genitourinary dysfunction - ED and neurogenic bladder • Gl dysmotility

Autonomic neuropathy

• Most common: oculomotor nerve • Pupil sparing oculomotor palsy • Median nerve - carpal tunnel syndrome • Ulnar mononeuropathy at the elbow • Fibular mononeuropathy at the knee • 6th and 7th nerve palsy • Pathophysiology: microvascular infarction

• Mononeuropathy

Most common mononeuropathy

Oculomotor n.

N on cts

Median n

Ulnar mononeuropathy at the

Elbow

Fibular mononeuropathy at the

knee

Pathophysio of mononeuropathy

Microvascular infarction

Subacute proximal leg weakness, asymmetric • Iliopsoas, quadriceps, adductors of hip • Accompanied by weight loss • Thigh pain • Most severe in femoral and obturator distributions with involvement of the knee flexor compartments

Diabetic amyotrophy

Damage to multiple thoracic nerve roots • Thoracic and abdominal pain • Abdominal pain and outpouching

Diabetic thoracoabdominal neuropathy

Diabetic Neuropathy tx

Optimal glucose control • Treatment guideline

• Usually produces sensory or sensorimotor neuropathy or mononeuropathy multiplex • Systemic disease has usually been diagnosed or is identifiable after work up • Often responds to immunomodulatory therapy Rheumatoid arthritis Polyarteritis nodosa Churg Strauss syndrome SLE Sjogren syndrome

Collagen Vascular Disease and Vasculitis

Collagen Vascular Disease and Vasculitis responds to

Immunomodulatory therapy

Hereditary Peripheral Neuropathies • 3 major categories:

1. Hereditary motor and sensory neuropathies (HSMN) 2. Hereditary motor neuropathies (HMN) 3. Hereditary sensory and autonomic neuropathies (HSAN) 4. Others

Hereditary Motor and Sensory Neuropathies (HMSNs) • Main features:

Charcot-Marie-Tooth (CMT) types 1 and 2 • Gradually progressive distal weakness, atrophy and sensory loss over many years • Foot drop is common presenting feature • Frequent hammer toe and pes cavus deformity • CMT type 1A is the most common variety (PMP22 reduplication)

• Weakness beginning in small foot and fibular muscles progressing to hand and forearm • Distal symmetric sensory loss • Paresthesias and cramps • Distal muscle atrophy • Griffe de orteils, inverted champagne bottle atrophy, equinovarus • Main en griffe (claw hand) • Pes cavus and hammer toes • Diminished or absent DTRs • No autonomic dysfunction

Hereditary Motor and Sensory Neuropathies (HMSNs)

• Autosomal dominant • Chronic demyelinating • CMT-1A - most common subtype • Reduplication of peripheral myelin protein 22 • 60% of all hereditary neuropathies • Enlarged palpable peripheral nerves especially greater auricular nerve • Nerve biopsy: onion bulb appearance of myelin due to constant demyelination and remyelination

СМ Type 1 (HMSN type 1)

СМ Type 1 (HMSN type 1) most common subtype

• CMT-1A

СМ Type 1 (HMSN type 1) nerve biopsy

onion bulb appearance of myelin due to constant demyelination and remyelination

• Autosomal dominant or autosomal recessive • Chronic axonal neuropathies • Nerve biopsy: neuronal loss without demyelination

•СМТ Type 2 (HSMN Type 2)

• Autosomal dominant or autosomal recessive • Demyelinating • Presents in infancy • Severe and disabling

• СМТ Туре 3 (Dejerine-Sottas Disease; HSMN Type 3)

Hereditary Motor and Sensory Neuropathies (HMSNS) Classification

Dyck and Lambert Classification of HMSN

Weakness and atrophy in lower extremities during adolescence and later progresses to the hands Slow nerve conduction velocities Distal weakness, mild sensory loss Palpable nerves Decreased reflexes

1a and 1b (most common) Autosomal dominant Hypertrophic demyelinating neuropathy

Onset in adolescence, symptoms similar to type 1 Nonpalpable nerves

2 Autosomal dominant Neuronal neuropathies

Onset in infancy with delayed motor skills, more severe than type 1 and 2 Autosomal recessive

3 Dejerine-Sottas Hypertrophic neuropathy of infancy

Muscle weakness and atrophy as in other types Autosomal recessive

4 Refsum Hypertrophic neuropathy associated with phytanic acid excess

Onset between 5-12 Lower legs affected first by muscle weakness and atrophy followed by upper extremities Associated with visual and hearing loss

5 Associated with spastic paraplegia

Early onset muscular weakness and atrophy followed by optic atrophy resulting in vision loss and possibly blindness

6 With optic atrophy

Later onset with muscular weakness and atrophy mostly in lower extremities

7 With retinitis pigmentosa

Hereditary Motor Neuropathies (HMNs) Main ft

• Pure motor weakness without sensory loss • Distal onset • Slowly progressive over years • Autosomal dominant inheritance • Less common than HMSNS

• Rare • Age 20-40 • Very slowly progressive distal weakness and atrophy • Normal life expectancy • NCS: pure motor, axonal neuropathy with normal velocities, reduced CMAP amplitude and normal sensory responses

Hereditary Motor Neuropathies (HMNs)

Main features: • Multiple compressive nerve injuries (els, ulnar at elbow, moular du knee • Mild, generalized demyelinating neuropathy may be present • Autosomal dominant but many have no family history • Presents in 20-40 yo • Multiple painless focal peripheral lesions • Treatment: • Avoiding risks for compression.

Hereditary Neuropathy with Predisposition to Pressure Palsy (HNPP)

Predominant pain and temperature loss in feet Onset in 2nd or 3rd decade Most prevalent of HSANS Acromutilation

1 AD SPTLC1

Loss of all sensory modalities in distal hands and feet Onset in infancy

2 AR HSN2

Riley-Day syndrome (familial dysautonomia) Ashkenazi Jewish descent Onset in infancy Poor temperature control Excessive sweating BP fluctuations

3 AR IKBKAP

Loss of all sensory modalities in distal hands and feet Onset in infancy

4 AR TRKA/NGF receptor

Congenital insensitivity to pain Onset in infancy Poor temperature control Anhidrosis Mild MR

5 AR None