10.3. Dorsal Root Ganglion Disorders
Malignant Inflammatory Sensory Polyganglionopathy (MISP)
- General features:
- Most common malignancy associated with the syndrome is small cell cancer of the lung (SCLC); variety of other tumors has been associated including Hodgkin's, prostate and breast
- All SCLC patients smoked
- In approximately 75% of patients neurologic syndrome preceded cancer by months
- In approximately 20% of patients, cancer preceded the neurologic symptoms
- Cytotoxic T cells may be involved in the pathology of the DRG and CNS structures
- Clinical patterns:
- Ataxic
- Ataxic-hyperalgesic
- Ataxic-hyperalgesic with gastric dysmotility
- The specific syndrome is related to the size of the involved DRG cells:
- Large diameter DRG cell involvement is associated with ataxia, vibratory and proprioceptive loss
- Small diameter DRG cell destruction causes hyperalgesia and loss of temperature sensibility
- Destruction of the myenteric plexus causes gastric dysmotility
- Clinical presentation:
- Generally subacute over days to weeks; occasionally it is abrupt over hours
- Ataxic variant often starts with paresthesias; gait unsteadiness; decreased fine motor control
- Ataxic-hyperalgesic patients often first note lancinating and burning extremity pain (C and A-delta fibers) followed by incoordination and loss of dexterity
- Ataxic-hyperalgesic form with gastric dysmotility presents with abdominal pain, N and V and constipation. Rarely is ataxia and limb pain noted initially although hyporeflexia and wasting may be present on exam.
- Neurologic examination:
- Normal strength or only mild weakness
- Proximal and distal large fiber sensitivity loss which may be asymmetric
- Hyporeflexia; lower greater than upper extremities
- Pseudoathetosis in severely affected patients with large fiber loss
- Sensory process may begin in the arm and face.
- Central signs associated with malignant inflammatory sensory polyneuropathy:
- Eye movement abnormalities (nystagmus and gaze palsy)
- Dementia and confusion
- Cerebellar ataxia
- VIIIth nerve dysfunction
- Urinary retention
- Babinski response
- Flaccid weakness and atrophy
- Dysgeusia
- Myelopathy
- Limbic encephalopathy
- Sensory involvement of the face and the trunk
- Laboratory evaluation:
- CSF:
- Normal to moderately elevated protein (mean 104–127 mg/dL in 16 patients)
- Minimal lymphocytic pleocytosis in a few patients
- Anti-neuronal neural antibodies ANNA-I (anti Hu antibodies); (react against neuronal nuclear protein antigens) are seen in approximately 2/3 of patients
- EMG:
- Low amplitude or absent SNAP
- Normal CMAP
- Occasional fibrillations
- MRI:
- Few patients demonstrated findings associated with associated limbic encephalitis
- Pathology:
- Inflammation early and later fibrosis of the DRG neurons; subsequent degeneration of posterior roots and myelinated sensory axons; degeneration of the posterior columns.
- Loss of neurons in the myenteric plexus
Non-Inflammatory Sensory Polyganglionopathy (MISP)
- General features:
- Most often associated with Sjögren's syndrome
- Other entities reported:
- Paraproteinemia
- Celiac disease
- EBV infection
- Pure sensory GBS
- Antibodies to chondroitin sulfate C or sulfatide
- Putative cell mediated immune attack on DRG
- Clinical presentation:
- Two major syndromes:
- Ataxic (large DRG neurons involved)
- Hyperalgesic (small diameter and autonomic neurons are involved)
- Mixture
- Subacute progressive onset; a few patients have explosive onset over hours
- Ataxic form:
- Paresthesias, unsteady gait, poor manual extremity, rarely painful
- Hyperalgesic variety:
- Burning and lancinating extremity pain are presenting symptoms. May be asymmetric and begin in the arms and face rather than the legs.
- Normal strength; distal and proximal large fiber sensory loss, diminished reflexes
- Autonomic involvement in some patients is manifested by abnormal Valsalva responses, Adie's pupils and arrhythmia
- Laboratory evaluation:
- CSF:
- Normal to slightly increased protein (early phase)
- No pleocytosis (rarely lymphocytic pleocytosis early)
- Sjögren's:
- Positive for extractable nuclear antigen SS-A; SS-B
- IgM-kappa, IgG kappa, IgA-kappa immunoglobulin monoclonal proteins have been described in some patients
- EMG:
- Absent low amplitude SNAP (disease distal to DRG)
- Normal or minimally decreased CMAP
- Needle EMG is usually normal; an occasional fibrillation potential noted in isolated muscles
- MRI:
- Cervical spinal cord increased signal on T2 weighted images (dorsal columns involvement in Sjögren's Disease)
- Pathology:
- Sural nerve demonstrates decreased density of large myelinated fibers; some axonal atrophy
- Inflammatory cells around DRG and in the endoneurium
Toxic Polyganglionopathy
- General features:
- Perforating arterioles from the epineural blood vessels penetrate the perineural sheath to supply the DRG. The capillaries of the DRG are fenestrated which results in easy diffusion from the blood to the endoneurium of DRG cells.
- Usual neurologic picture of DRG toxic disease is:
- Proximal and distal sensory loss
- Hyporeflexia
- Slow recovery after toxic exposure
Cisplatin (cis-diamminedichloroplatinum(II)) (CDDP)
- General features:
- Neurotoxicity occurs from involvement of the DRG or its axons
- Does not cross the blood brain barrier (BBB); access to the DRG from the serum through fenestrated capillaries of the epineural blood vessels.
- Myelosuppression, nephrotoxicity and damage to cochlear hair cells are expected complications.
- Neurotoxicity occurs greater than 400–500 mg/m2. Coasting effects is often noted (symptoms persist or sometimes start after the drug is stopped)
- Putative mechanism of action:
- CDDP binds to neuronal DNA and induces apoptosis
- Toxic level may be as low as 100 mg/m2
- Clinical presentation:
- Neuropathy is related to total cumulative dose
- Insidious onset with distal lower extremity paresthesias greater than upper extremities
- Symptoms may begin proximally and evolve into severe sensory ataxia
- Some patients report painful paresthesia
- Lhermitte's sign may be noted; thermal sensitivity is usually spared
- Mild peripheral muscle weakness
- Improvement occurs if the total dose is less than 500 mg/m2
- EMG:
- Decreased SNAP's; increased distal latency; N SNCV and CMAP; severe cases have abnormal somatosensory evoked potentials (SEP)
Pyridoxine
- General features:
- High doses cause loss of DRG neurons, axons and fibers in the dorsal columns
- Clinical presentation:
- Toxic dose 2–6 g/day; minimum daily requirement is 2 mg/day
- Progressive ataxia starts within weeks to months on a dose of 2–6 gm/day
- Numbness and paresthesias are seen on doses of 250 mg to 2 gram/day which is reversible
- Complete deafferentation has been noted with IV doses of 132 and 183 gram over three days
- Gait ataxia
- Loss of kinesthetic sensations
- Hyporeflexia with normal strength
- EMG:
- Reduced or absent SNAPs; low amplitudes of NCVs
- Delayed central sensory conduction by SEP (somatosensory evoked potentials)
- Laboratory:
Central Sensory Syndrome (Toxic Polyganglioneuropathy)
- Definition:
- Dysfunction limited to the central posterior column axon segment of large DRG cells
- Differential Diagnosis:
- Compressive posterior column myelopathy:
- Cervical spondylosis
- Spinal stenosis (congenital or acquired)
- Posterior longitudinal ligament calcification (oriental patients)
- Holmes–Adie syndrome
- Ocular
- Tonic contraction to light and to accomodation
- Posterior column ataxia of Biemond
- Subacute myelo-optic neuropathy (clioquinol intoxication)
- Tabes dorsalis
- Vitamin E deficiency
- Clinical presentation:
- Kinesthetic and vibratory sensory loss
- Ataxia
- Hyporeflexia
- Poor tandem gait (particularly with cervical stenosis and spondylosis)
- EMG:
- Normal sensory and motor NCV
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