Differential Diagnosis in Neurology

Topic 10. Differential Diagnosis of Peripheral Neuropathy

10.11. Immune Mediated Neuropathies

Acute Inflammatory Polyneuropathy (AIDP; Guillain Barré Syndrome)

  • General features:
    • Most common acute areflexic cause of quadriparesis
    • 0.6–2.4 cases/million person per year/USA
    • Preceding illness; infections, surgery, trauma, immune dysfunction, systemic illness
    • Specific conditions:
      • After seroconversion in HIV (lymphocytosis in CSF)
      • In the face of immunosuppression (following transplantation)
    • CMV (possibly 15% of patients):
      • Younger patients; severe course; respiratory failure; frequent cranial nerve involvement; antibodies against GM2
    • EBV (10% of patients); mononucleosis; pharyngitis or hepatitis
    • Campylobacter jejuni is the most common infection preceding GBS (possibly 30% of patients) axonal loss; elevated GM1 antibodies protracted recovery. Epitopes involved in the molecular mimicry are: GM1; GQ1b; Gal NAc-GD1a.
    • Mycoplasma (approximately 5% of patients) fever, headache and dry cough, cold agglutinin in serum
  • Clinical presentation:
    • Symmetrical leg weakness; proximal usually greater than distal; foot drop rarely seen early; 10% upper extremity greater than lower extremity weakness; 60% lower extremity greater than upper; approximately 30% are equally affected. Descending weakness in 14% of patients. Rare fasciculation or myokymia
    • Differential points as regards weakness; in contrast to muscle or neuromuscular diseases distal muscle weakness develops after proximal muscle involvement.
    • Onset to maximal motor deficit and plateau:
      • Average 17–20 days
      • 40% After the first week
      • 80% after the second week
      • 90% by third week
    • Sensory symptoms:
      • Early distal numbness and paresthesias
      • Minimal sensory deficit
      • Severe muscle, back and extremity pain in 50%; may be seen up to 80% with time
      • Rarely back and radicular pain precede weakness
      • Sensory level on the trunk but no analgesia below the level
      • Sensory ataxia early prior to weakness
    • Cranial nerve involvement:
      • Symmetrical peripheral facial weakness occurs in approximately 60–70% of patients; rarely it is unilateral often the weakness is asymmetric; more often with severe extremity weakness
      • Quadriparesis without facial weakness is very rare
      • 10–20% of patients have partial or complete ophthalmoparesis
        • VIIth nerve most commonly affected bilaterally greater than unilaterally
      • Oropharyngeal weakness in 50%
    • Respiratory paralysis in 30% apparent by two weeks
    • Urinary retention for 1–2 days in about 2% of patients associated with spinal paresthesia
    • Fecal incontinence occurs in 1% of patients
    • Autonomic dysregulation:
      • Common
      • Occurs with quadriparesis and ventilatory support most commonly
      • Manifestations:
        • Sinus bradycardia
        • Sinus arrest
        • Variety of supraventricular arrhythmias
        • Paroxysmal hypertension or hypotension
        • Vagal episodes:
        • a) Bronchorrhea, bradycardia, hypotension
      • Ileus
      • Peripheral vasomotor instability; cyanosis and livedo reticularis
    • Areflexia or hyperreflexia within one week
    • Diminished or absent reflexes in a paretic limb by three days
    • AIDP can occur at any point during pregnancy

Unusual Features within the Classic Presentation

  • Unilateral paralysis
  • Radicular pain and weakness at onset
  • Severe neck, back and extremity pain, deep ache, mechanical and thermal allodynia, hyperalgesia ("meningitis variant")
  • Severe generalized burning, pain ("C" fiber)
  • Central features: optic neuritis; hyperactive reflexes at onset
  • Babinski sign
  • Early and almost pure respiratory failure
  • Early severe vibration and position sense loss (sensory ataxia)
  • Conjugate recovery of ophthalmoplegia; recovery of upgaze earlier than horizontal gaze; preservation of Bell's phenomenon with impaired voluntary gaze
  • Preserved triceps reflex
  • Increased intracranial pressure:
    • Bilateral papilledema
    • Increased CSF protein
    • Cytotoxic intracranial edema (Joynt hypothesis)
    • Blockage of pacchionian granulation (Denny–Brown hypothesis)
    • Respiratory paralysis; PCO2 greater than 70 mmHg
  • Severe ataxia (Richter's variant):
    • Primary involvement of large peripheral nerve fibers or the DRG
    • Severe ataxia of the upper and lower extremities
    • Less loss of position sense than expected; abnormal spindle afferent input to the cerebellum
    • Sensory ataxic tremor
  • Transverse Myelitis:
    • Transverse myelitis
    • Concomitant with onset of the peripheral neuropathy
    • Bowel and bladder involvement
    • Reflexes in arms greater than legs

Axonal Forms of GBS

Acute motor sensory axonal neuropathy (AMSAN)

  • General features:
    • Axons are the target of the immune response
    • Nerve inexcitability
    • Rapid progressive paralysis
    • Ventilatory assistance
    • Distal sensory loss
    • Poor recovery
    • Elevated CSF protein
    • Quadriplegic within days after onset
    • Poor recovery
  • EMG:
    • Denervation
    • Inexcitable nerves
  • Pathology:
    • Axonal degeneration
    • No demyelination of the motor nerves

Antecedent Illnesses Preceding GBS (AIDP)

  • Precedent illnesses can be identified in approximately 2/3 of AIDP patients:
    • Average interval to onset is 11 days (1–3 weeks)
    • Greater than 5–6 weeks possible, but less likely causative
  • Most common is uncharacterized upper respiratory illness; recent, Campylobacter pylori infection with diarrhea is responsible for approximately 20% of patients
  • Ten percent of patients with abnormal liver enzyme profile from putative hepatitis from CMV, EBV, hepatitis (A, B, C)
  • HIV associated AIDP; lymphocytic pleocytosis to 40 cells/mm3; occurs at the time of seroconversion from ARC.
  • CMV and EBV associated with concomitant pharyngitis, headache and GI symptoms
  • Mycoplasma; pneumonia, dry cough, fever, pharyngitis and cold agoutis.
  • Usual vaccination associated; small pox, rabies, hepatitis, polio, swine flu
  • Post-surgical AIDP:
    • 2–3 weeks after an operation
    • Associated with abdominal, intracranial, thoracic and orthopedic procedures
    • Rarely associated with spinal operations

Medical Complications of GBS

  • General features:
    • Arrhythmias:
      • Occur in 10–80% of patients
      • Sinus tachycardia (30–60%)
      • Sinus brady cardia (10–30%)
      • Premature ventricular and atrial contractions
      • Ventricular tachycardia and asystole rare except in the autonomic variant
    • Mild or asymptomatic glomerulonephritis
    • Inappropriate ADH in 7–25% of patients (usually serum sodium of between 120–130 meq/dl)
    • Diabetes insipidus (rare)
    • Ileus and gastric retention (>40%)
    • Compression mononeuropathy; peroneal and ulnar nerves
    • Pseudotumor cerebri (1–3%)
    • Rare pulmonary emboli
  • EKG:
    • Abnormalities in 50–80% of patients
    • Depressed ST segments; inverted T-waves; varying R-R intervals
  • EMG evaluation:
    • Prolonged distal motor latencies early in the course
    • Conduction block with >20% progressive reduction in CMAP (30% of patients)
    • Slowing of motor nerve conduction with dispersion of the wave form; conduction velocities become slower during recovery due to remyelination
    • Slowed sensory nerve conduction velocities by three week of illness in 75% of patients; decreased sensory amplitudes
    • Median and ulnar sensory potentials are reduced or absent when the sural nerve is normal
    • Fibrillations in 20–64% within the first four weeks
    • CM Fiber variant:
      • Reduced or absent sensory potentials with normal motor studies
    • Abnormal spontaneous activity noted in 2–4 months in affected muscles
    • Myokymia may be seen in the face and extremities early in illness
    • Axonal forms of GBS:
      • Reduced or absent motor and sensory potentials; inexcitable nerves
    • AMAN has normal sensory potentials

CSF Abnormalities of GBS

  • Cytoalbuminologic dissociation in 80–90% of patients
  • In general, 5 lymphocytes; occasionally up to 20 lymphocytes; the more cells noted the more likely another problem such as lymphoma, carcinomatosis, or leukemia is involving the nerve roots; HIV and Lyme are the exception and may demonstrate greater than 40 lymphocytes/mm3.
  • Protein elevation:
    • Starts approximately day 3–10
    • Usual levels are 100–180 mg/dl; extremely rare to note greater than 500 mg/dl (this level suggests a spinal block; Freund's reaction)

The Differential Diagnosis of Acute Inflammatory Demyelinating Polyneuropathy (AIDP)

The diagnosis of AIDP in general is very straight forward. However, patients may present without an obvious history or with associated neurological or medical problems that alter their mental status.

A high cervical spinal cord injury causes flaccid quadriparesis, loss of bowel and bladder control, hypothermia (97 degree Fahrenheit) and hypotension. Acute inflammatory myopathy is often associated with sore muscles, rare diaphragmatic weakness, depressed, but intact reflexes and no bowel or bladder dysfunction. Metabolic muscle disease, the periodic paralysis's, hypophosphatemia, hypercalcemic states spare the cranial nerves, bowel and bladder. They are areflexic and are clear mentally. Myasthenia gravis usually affects the facial muscles more than the muscles of mastication, has no sensory loss and normal pupils. Hyperkalemia has normal mentation, no bowel or bladder dysfunction and inexcitable reflexes or muscle. Toxic neuropathies often have concomitant CNS involvement.

Acute Peripheral Neuropathies

Toxic Neuropathies

  • General features:
    • History of exposure
    • Involvement of other organ systems
  • Clinical seminal features:
    • Thallium (hair loss; distal extremity pain)
    • Arsenic (hyperkeratosis, GI symptoms)
    • Lead (encephalopathy, hypertension, abdominal pain)
    • N-hexane (encephalopathy)

Differential Diagnosis of Acute Demyelinating Neuropathies

  • Drugs:
    • Amiodarone: painful, skin changes
    • Perhexiline: lumbosacral roots
    • Gold: rash; intrinsic hand muscle
    • Alcoholics: axonal destruction
    • Vincristine/vinblastine
    • Gold
    • Chloroquine
    • Mevacor (all cholesterol lowering agents)
    • Emetine
    • Dideoxycytidine (ddC)
    • AZT
    • Disulfiram
    • Nitrofurantoin
    • INH
  • Infection:
    • Diphtheria
    • Tick paralysis
    • Poliomyelitis
    • Lyme disease
    • Rabies (pharyngeal-cervical variant)
    • HIV
  • Metabolic:
    • AIP
    • Variegate porphyria
    • Coporphyrinuria hypermagnesemia
    • Hypophosphatemia (less than 2 mg/dl)
    • Uremia (hyperkalemia K+ > 6 mg/dl
    • Secondary hypokalemic periodic paralysis
    • Renal tubular acidosis
    • Diuretics acidosis
    • Hyperaldosteronism
  • Toxins:
    • Most organophosphate insecticides
    • Hydrocarbons
    • Buck thorn
    • Toluene
    • Solvents
  • Autoimmune processes:
    • Demyelinating disease (CIDP) spinal cord
    • Peripheral nerve involvement from vasculitis

Differential Diagnosis of Acute Quadriparesis

  • Periodic paralysis:
    • hypokalemic;
    • lid retraction, no myotatic reflex
  • Tick paralysis: ataxia then weakness and areflexia
  • Organophosphates: miosis, sweating, seizures
  • Myasthenia gravis:
    • Cranial nerve involvement
    • Reflexes are spared
  • Botulism:
    • Ptosis
    • pupillary dilatation
    • pharyngeal paralysis
    • GI symptoms
  • Polymyositis: painful, swollen muscle, reflexes present
  • Critical care neuropathy (three weeks in ICU):
    • Sepsis
    • Multiorgan involvement
    • Difficult to wean off respirator

Differential Diagnosis of Acute Quadriparesis with Severe Pain

  • AIP:
    • Acute abdominal pain
    • Soft abdomen autonomic dysfunction
    • Nondermatomal patchy sensory loss
  • Thallium:
    • Acute vascular collapse
    • Distal weakness
    • Late alopecia
  • Arsenic:
    • Distal extremity weakness
    • Hyperkeratosis of palms and soles
  • Vasculitis:
    • Distal extremities
    • Associated medical problems such as asthma, eosinophilia
  • Mononeuritis multiplex:
    • Underlying autoimmune cause
    • Quadriceps pain in femoral nerve infarction

Differential Diagnosis of Acute Neuropathy with Prominent Sensory Abnormalities

  • Acute sensory neuropathy
    • Dorsal column functional loss
    • Large fiber modalities
  • Rabies (simulating the pharyngeal, cervical, brachial variant of GBS)
    • Pharyngeal spasms
    • Muscle pain
    • Motor neuropathy
  • Vasculitis neuropathies
    • Mononeuritis multiplex
    • 15% distal symmetrical involvement
  • Ciguatera toxin
    • Burning pain, large joint involvement, mouth involved
    • Paradoxical temperature perception
  • Thallium
    • Alopecia
    • Distal pain
  • Arsenic
    • Hyperkeratosis
    • Burning distal extremity pain
    • Vascular collapse
  • Perhexiline (lumbosacral root involvement)
  • Paralytic
    • Shell fish: domoic acid
    • Small fiber neuropathy
    • GI symptoms

Differential Diagnosis of Increased CSF Protein and Acute Neuropathy

  • Carcinomatous meningitis
  • Leukemia and lymphomatous meningitis
  • Arsenic
  • Lead
  • Vincristine
  • Perhexiline
  • Thallium

Differential Diagnosis of Disorders of the Neuromuscular Junction Simulating (AIDP)

  • MG
    • Reflexes retained
    • Cranial nerve involvement
  • Botulism
    • Internal ophthalmoplegia
    • Nasopharyngeal weakness > ophthalmoplegia
  • Snake envenomations
    • Pain at the site
    • Perioral numbness
    • Pharyngeal paralysis
  • Hypermagnesemia
    • No myotactic reflexes
    • Cranial nerves spared
  • Gentamicin
    • Setting of gram negative infection
    • Less cranial nerve involvement
  • Tetanus
    • Opisthotonus, pharyngeal and masseter spasm
  • Succinylcholine
    • prolonged exposure
    • Failure to move after surgery

Differential of Acute Myopathy Simulating AIDP

  • Polymyositis
    • No VIIth nerve involvement
    • Reflexes relatively preserved
  • Acute rhabdomyolysis
    • Severe edema of affected muscles
    • Skin blisters
    • Pain
  • Critical care myopathy
    • Often associated with axonal neuropathy
    • Hard to wean from respiratory
    • Diaphragmatic involvement

Differential of CNS Abnormalities Simulating AIDP

  • Acute transverse myelitis
  • Intrinsic Cervical cord disease
    • cavernous hemangioma
    • Acute disseminated encephalomyelitis (ADEM)
    • bleed
  • Rhombencephalitis
    • Herpes simplex seen in 6 HIV patient
    • CMV (lumbosacral roots prominently affected)
    • Listeria (pregnancy, ENT surgery, dorsal pons involvement)
  • Locked in syndrome
    • Vertical gaze intact
    • No horizontal eye movements
    • Quadriplegia
  • Basilar artery infarction
    • Pin point pupils
    • Herald hemiparesis
    • May have prominent sensory loss

Acute Motor Axonal Neuropathy (AMAN)

  • General features:
    • Primarily in children
    • Most patients affected in Spring epidemics in Northern China
    • Prior Campylobacter jejunum infection
    • Neurological features preceded by gastrointestinal symptoms
    • Symmetric limb weakness
    • Oropharyngeal and respiratory muscle weakness
    • No sensory loss
    • No extraocular muscle involvement
    • Facial diplegia is common
    • Areflexia
    • Rapid recovery in some patients
  • EMG:
    • Reduced or absent motor unit potentials
    • Normal motor, nerve conduction velocities
  • Laboratory:
    • CSF protein elevated
    • Elevated antibody titers to C. jejunum, anti-DM1 and Anti-GalNAc-GD1a
  • Pathology:
    • Axonal degeneration
    • Macrophages in the periaxonal spaces

Pure Motor Variant of AIDP (GBS)

  • General features:
    • Probably less than 5% of GBS patients
    • Preceding C. jejuni infection
    • High anti-GM1 antibody titers
    • Elevated CSF protein greater than 45 mg/dl within
  • Clinical features:
    • Progression of weakness over one day to four weeks
    • Symmetric weakness in the extremities
    • Generalized hyporeflexia or areflexia within one week
    • No paraesthesias or sensory loss
    • No cranial nerve involvement
  • EMG:
    • Axonal features
      • Absent, impersistent or dispersed F-waves in at least two limbs
      • Or motor NC block or slowing (<80% of normal)
      • Or SNAP
  • Differential diagnosis:
    • Lead poisoning (usual hypertension, increased ICP, stomach pains)
    • MG (cranial nerve involvement; intact reflexes)
    • Acute intermittent porphyria (abdominal pain, autonomic dysregulation, wasting)
    • Tick paralysis (ataxia > weakness)

Sensory Variant of GBS (AIDP)

  • General features:
    • Rare
  • Clinical presentation:
    • Abrupt onset
    • Rapid progression
    • Large fiber modality involvement greater than small fiber
    • Sensory ataxia (decreased vibration and proprioception sensibility
    • Paresthesias in feet and hands at onset
    • Radicular features occur in some patients
    • Proximal progression of sensory loss over days to one month; face frequently affected early with paresthesias around the mouth
    • Improvement of sensory parameters within 1–2 months after onset
    • No weakness or respiratory failure
    • Generalized hypo or areflexia within one week
    • CSF protein elevation (>45 mg/dl within 1–3 weeks)
  • EMG:
    • Severe diminution of sensory nerve conduction velocities
    • Minimal slowing of motor NCV

Miller–Fisher Variant of AIDP (GBS)

  • General features:
    • Approximately 5% of GBS patients
    • May evolve to generalized GBS
    • C jejunum infection as well as other viral infections may precede illness
  • Clinical features:
    • Diplopia often the first symptom; VI nerve weakness often evolves to complete ophthalmoplegia
    • Ptosis bilateral and symmetrical; rarely it is accompanied by internal ophthalmoplegia
    • Ataxia of all limbs; gait is impaired
    • Loss of reflexes by one week
    • Cerebellar outflow tremor
    • Minimal or absent flaccid or pharyngeal weakness
    • Minimal or absent paraesthesia
    • Absent Babinski signs
    • Usually good recovery in six weeks
  • EMG:
    • Absent sensory nerve action potentials
    • Minimal or no deficits in motor NCV
  • Laboratory:
    • Increased antibodies to GQ1b, epitopes;
      • Paranoidal regions of III, IV, VI nerves are enriched with these epitopes
    • CSF: slightly elevated protein

Pharyngeal-Cervical-Brachial Variant (Munsat's Variant)

  • General features:
    • Regional pattern of involvement; descending paralysis
  • Clinical presentation:
    • Weakness limited to pharyngeal and neck muscle with subsequent appendicular spread; legs are spared early
    • Ptosis is common
    • Severe swallowing and respiratory embarrassment
  • EMG:
    • NCV normal early; demyelinating features noted later in the upper extremities
    • Blink reflexes may be positive
  • Laboratory:
    • Increased levels of Gal Nac-GD1a antibodies
    • Slightly elevated CSF protein

Leg Weakness Variant AIDP (GBS)

  • General features:
    • Isolated leg weakness and areflexia suggestive of cauda equina or spinal cord involvement
  • Clinical presentation:
    • Ocular, facial, oropharyngeal muscles spared
    • Arms are normal
    • Radicular leg pain is common; other sensory features are inconsistent
    • Bowel and bladder are spared
  • MRI of lumbar spinal roots: may demonstrate gadolinium enhancement
  • EMG:
    • Demyelinating features

Partial Post Infectious Peripheral Neuropathy

  • General features:
    • Abrupt onset
    • Bilateral in one region
    • Evolve over days to weeks
    • Monophasic
    • Associated with an elevated CSF protein
    • Demyelinating characteristics on EMG
  • Clinical presentation:
    • Acute distal weakness without severe sensory loss or cranial nerve involvement. The epitope is N-acetylglucosamine-GDIA
    • Acute ataxia
    • Facial diplegia with or without VIth nerve palsy and distal paresthesia
    • Asymmetric ocular nerve palsies
    • Isolated cranial nerve X (EBV)
    • Peroneal palsies with hand paraesthesias

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

  • General features:
    • Heterogenous group of neuropathies
    • Core feature is recurrent multifocal demyelination of peripheral nerve
  • Clinical presentation:
    • Onset and relapses often triggered by infections; approximately 80% of patients
    • Relapsing; monophasic or progressive course
    • Mean age of patients (30–50) all decades; males > females
    • Triggers in approximately 30% of patients:
      • Infection
      • Vaccination
      • Surgery
      • Trauma
    • Eight week duration of initial illness (AIDP no longer than 4–6 weeks)
    • Usually the onset of weakness is in the lower extremities
    • Some degree of numbness or paresthesias; occasionally painful (14–20%)
    • Proximal weakness equal or at times greater than distal
      • Legs > than arms
      • Neck flexors may be involved
    • Facial muscles rarely affected
    • Approximately 6% present with pure sensory involvement; 10–20% with pure motor involvement
    • Papilledema has been reported (CO2 narcosis)
    • Touch and vibration sensibility most affected; some have severe ataxic proprioceptive loss
    • Rare cranial nerve involvement that includes facial numbness, dysphagia, diplopia, ptosis
    • Decreased or absent reflexes in majority of patients
  • EMG:
    • Motor NCV decreased in two or more motor nerves
    • Conduction block or abnormal temporal dispersion in one or more motor nerves
    • Prolonged distal latencies in two or more nerves
    • Absent F waves or prolonged F wave latencies in two or more motor nerves
    • Supportive, but not necessary: absent H reflexes or reduction in sensory NCV less than 80% of the lower limit of normal
  • MRI: enhancement of involved nerve roots (unusual)
  • Laboratory:
    • CSF: increased protein (130–145 mg/dl)
  • Pathology (sural nerve biopsy):
    • Demyelination in most patients:
      • Approximately 20% are axonal
      • 15% mixed pattern

Differential Diagnosis of CIPD Associated with Concurrent Illness

  • Malignancy:
    • Adenocarcinoma
    • Cholangiocarcinoma
    • Seminoma
    • Pancreatic adenocarcinoma
    • Malignant melanoma (most common)
  • HIV
  • Chronic active hepatitis (B)
  • Some CIDP patients have central demyelinating lesions similar to multiple sclerosis
  • Diabetes mellitus

CIDP Associated with Monoclonal Gammopathy of Undetermined Significance (MGUS)

  • General features:
    • Definition: low levels of serum M protein
    • Exclusion of:
      • Anemia
      • Bence Jones protein in the urine
      • Bone lesions
      • Plasma cell count of greater than 5%
    • IgM antibodies noted against MAG epitopes
    • CIDP (MG US may have IgG or IgA, and IgM antibodies)
  • Clinical presentation:
    • Slower progression than idiopathic CIDP
    • Associated with anti-MAG antibody:
      • Incidence: 1–5/100,000 people
      • Greater than 90% are IgM monoclonal antibodies: IgM-MAG antibodies
      • Demyelination: IgM and complement found in myelin sheath; IgM-Kappa monoclonal proteins
  • Clinical presentation:
    • Males greater than females
    • Age of onset 40–80
    • Predominantly sensory dysfunction greater than 50% of patients; a few patients may have a predominantly motor neuropathy
    • Sensorimotor neuropathy presentation is common; action tremor often noted
    • Possible correlation of IgM-anti-MAG and anti MGAG-SGPG antibody with a preceding CMV infection
    • May develop a lymphoproliferative malignancy months to years after onset
  • EMG:
    • Slowed motor and sensory conduction velocities
    • Possibly IgM, MGUS different than IgA or IgG MGUS:
      • More frequent sensory loss and ataxia
      • Greater progressive over time
      • Higher frequency of nerve conduction deficits

Lewis–Sumner Syndrome

  • General features:
    • Acquired asymmetric sensorimotor polyneuropathy
    • Demyelinating
    • Multifocal conduction block in motor nerves
  • Clinical presentation:
    • Age at presentation varies, 20–80; mean in 6th decade
    • Slowly progressive course over years
    • Arms involved earlier than legs
    • Asymmetric involvement of discrete nerves
    • Weakness and numbness predominate; rare painful presentation
    • Rare cranial neuropathy
    • Reflexes are depressed more often they are than absent
  • EMG:
    • Multifocal demyelination of motor nerves
    • Prolonged distal latency, temporal dispersion and conduction block; asymmetric prolongation of F waves
    • Active and chronic denervations
  • Pathology:
    • Demyelinating and remyelinating aspects of the neuropathy
    • Normal CSF to slightly elevated protein

Multifocal Motor Neuropathy (MNN)

  • General features:
    • Slowly progressive, asymmetric multifocal weakness
    • Atrophy
    • No sensory loss
    • Multifocal conduction block
    • 50% have elevated anti GMI antibodies
  • Clinical presentations:
    • Onset from 20–70 years of age
    • Men > women
    • Gradually progressive asymmetric weakness
    • Upper extremity > lower extremity; distal muscle predominance
    • Weakness out of proportion to atrophy
    • Decreased reflexes in affected areas
    • Progressive course
  • EMG:
    • Conduction block
    • Temporal dispersions
    • Slowed motor NCVs
    • Prolonged distal latencies
    • Prolonged F wave latencies
    • Decreased conduction velocity in two or more motor nerves
  • Laboratory:
    • Antibodies agent GM1 ganglioside positive in high titers in greater than 50% of patients
    • Usually are IgM in class and are polyclonal
    • 10–15% of patients with very high titers of IgM-M protein is demonstrated by immunofixation
    • Serum may react with SG PG sulfa-glucuronyl paragloboside antibodies and may associated with a GD1a ganglioside
  • Pathology:
    • Demyelinations and axonal degeneration of motor nerves

Probable CIDP with or without Systemic Disease

  • Clinical presentation:
    • Progressive or relapsing motor and sensory involvement of two extremities developing over two months; may be motor or sensory alone
    • Hypo or areflexia of all limbs
  • Supportive of the diagnosis:
    • Proprioceptive, vibration or light touch sensory disability > loss of pain or temperature
  • Exclusion criteria:
    • Mutilation of hands or feet
    • Retinitis pigmentosa
    • Ichthyosis
    • Drug or toxin exposure
    • Genetically identified neuropathy
  • CSF studies:
    • Cell count of <10 mm3 if HIV seronegative; <50 mm3 if HIV is seropositive
    • Negative VDRL

Differential Diagnosis between CIDP, Lewis Sumner Disease and MMN

  • CIDP is symmetrical; childhood forms are noted:
    • Sensory loss occurs in stocking and glove distribution
    • V1–V2 facial involvement occurs often prior to attacks
    • Remitting and relapsing course
    • Rare GM1 antibodies
    • CSF (elevated protein)
  • Lewis–Sumner Disease:
    • Upper extremities affected first
    • Asymmetric presentation
    • Sensory loss occurs
    • Progressive course
    • Rare GM1 antibodies
    • CSF elevated protein
    • Decreased reflexes
  • MMN:
    • Men more common than women
    • No or minimal sensory loss
    • Asymmetric
    • 50% high antibody titers to GM1
    • CSF (often normal levels of protein)
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