Flashcards in CN LANGE - Sensory Disorders II Deck (73):
Granulomatosis with polynagiitis (Wegener):
Mononeuropathy multiplex or polyneuropathy occurs in up to 30% of cases.
1. Entrapment neuropathy in approx. 45% of patients.
2. Distal symmetric sensorimotor polyneuropathy in about 30%.
3. Mononeuropathy multiplex is a frequent feature in cases complicated by necrotizing vasculitis.
1. Neuropathy occurs in up to 20% of patients.
2. MC pattern is distal, symmetric, sensorimotor polyneuropathy.
3. Guillain-Barre can also occur.
+ Mononeuropathy simplex/multiplex --> Ulnar, radial, sciatic, or fibular nerve.
Involves peripheral nerves in 20% of cases.
--> Distal symmetric sensorimotor polyneuropathy is MC.
Scleroderma and mixed connective tissue disease:
Cranial mononeuropathy --> Most often involves the trigeminal nerve.
Which collagen vascular disease is not commonly associated with polyneuropathy?
Progressive systemic sclerosis.
Neoplastic and paraproteinemic neuropathies:
1. Nerve compression is a common complication of MM, lymphoma, and carcinoma.
2. Tumorous invasion of the EPINEURIUM may occur with leukemia, lymphoma, and various cancers, particularly carcinoma of the breast or pancreas.
Paraneoplastic syndromes - Sensory or sensorimotor polyneuropathy:
1. Occurs with both carcinoma and lymphoma.
2. Sometimes asymmetric + may accompanied by pain.
3. CSF is TYPICALLY ACELLULAR - Protein may be mildly elevated.
Among patients with chronic sensorimotor polyneuropathy of uncertain cause, approx. ...?
10% have a monoclonal gammopathy.
Paraneoplastic syndromes - Sensory neuroNOpathy:
1. Carcinoma can cause it.
2. Anti-Hu (or ANNA-1).
--> May be the presenting manifestation of cancer.
Paraneoplastic syndromes - Motor neuroNOpathy, Guillain-Barre, and other motor disorders:
1. Lymphoma may be complicated by motor neuronopathy (anterior horn cells).
2. HL + Angioimmunoblastic lymphadenopathy are sometimes associated with Guillain-Barre.
3. Lambert-Eaton, neuromyotonia, stiff-person syndrome.
Paraneoplastic syndromes - Autonomic neuropathy:
1. May occur especially in patients with small-cell lung cancer.
2. Anti-Hu + Anti-ganglionic ACh receptors (Anti-nAChR).
3. Underdiagnosed, often develops in the setting of other paraneoplastic syndromes, and has a poor prognosis.
4. Affected patients do NOT improve with immunotherapy even after treatment of the underlying tumor.
Paraproteinemias - Patients with paraproteinemic demyelinating neuropathy, especially a chronic distal sensory neuropathy, may have ...?
Malignant plasma cell dyscrasia.
The paraprotein is likely to underlie the neuropathy when it is an ...?
--> When it is IgG or IgA, the neuropathy may be clinically + electrophysiologically indistinguishable from CIDP and similar in its response to treatment.
Polyneuropathy in LYTIC MM:
Distal symmetric sensorimotor polyneuropathy.
--> Usually affects men.
--> All sensory modalities are affected, pain is a frequent feature, and the reflexes are depressed.
--> DEATH within 2 years.
Polyneuropathy and sclerotic MM:
1. Chronic demyelinating polyneuropathy.
2. MOTOR involvement predominates, but vibration and position sense may also be impaired.
3. Reflexes are depressed.
4. Pain is less common.
5. Symptoms may improve with treatment of the underlying cancer or by plasmapheresis.
4. M protein.
5. Skin changes.
--> May complicate plasma cell dyscrasias, especially osteosclerotic myeloma.
POEMS syndrome - Sensorimotor neuropathy may show certain distinctive electrophysiologic features, such as ...?
Slowing that is MORE MARKED in INTERMEDIATE than distal nerve segments.
A sensorimotor polyneuropathy similar to that observed with LYTIC MM may also occur in ...?
1. Waldenstrom macroglobulinemia.
2. Benign monoclonal gammopathy.
Toxic neuropathies - Alcoholism - Controversy exists concerning ...?
The relative contributions of direct neurotoxicity of alcohol + associated nutritional (especially thiamine) deficiency in producing polyneuropathy.
Alcoholic polyneuropathy is typically ...?
A symmetric distal sensorimotor polyneuropathy.
Pyridoxine toxicity may cause ...?
A sensory neuroNOpathy that disproportionately impairs vibration and position sense.
Hereditary neuropathies - Hereditary motor and sensory neuropathies (HMSN):
Charcot-Marie-Tooth (CMT) hereditary neuropathies.
--> Genetically heterogenous group of disorders having a similar clinical phenotype.
--> Weakness and wasting of distal muscles in the limbs +/- sensory loss.
+ Pes cavus and reduced or absent tendon reflexes also occur.
CMT hereditary neuropathies are divided into:
1. Demyelinating (CMT-1).
2. Neuronal (CMT-2) --> Spares sensory neurons and resembles progressive SMA.
CMT - BOTH types have an ... inheritance pattern.
CMT-1 - Clinical features:
1. Onset: 1st decade.
2. Slowly progressive course - variable severity.
3. Nerves are often palpably thickened.
4. Nerve conduction velocities are often markedly reduced.
CMT-1 - Genetics:
It is subdivided on the basis of the genetic findings, BUT the MC form results from duplication of or mutations in the gene for peripheral myelin protein 22 (PMP22).
CMT-2 - Clinical features:
1. Generally less severe than CMT-1.
2. Normal or near-normal nerve conduction velocities.
3. Does NOT cause nerve enlargement.
CMT-2 - The MC mutations are in genes for ...?
Kinesin family member 1B (KIF1B) and mitofusin 2 (MFN2).
--> X-linked dominant (CMT-X) and AR (CMT-4) variants have also been described.
1. Onset by 2 years of age with delayed MOTOR milestones.
2. Severe sensorimotor neuropathy that frequently extends to the proximal muscles and is associated with skeletal abnormalities such as scoliosis.
3. SEVERE DEMYELINATION of the nerves.
CMT-3 inheritance pattern:
AR or AD - Same genes with CMT-1.
Hereditary sensory and autonomic neuropathies (HSAN) - Type I:
2. Gradually progressive course from early adulthood.
3. Symmetric loss of distal pain/temp perception.
4. Relative preservation of light touch.
5. Tendon reflexes depressed.
6. LITTLE MOTOR DISTURBANCE.
HSAN type I - Mutations:
1. Genes for serine palmitoyltransferase long-chain subunits (SPTLC1, SPTLC2).
2. GTPase atlastin family (ATL1, ATL3).
3. DNA methyltransferase 1 (DNMT1).
2. Onset is in infancy/childhood.
3. Progression is slow.
4. ALL sensory modalities are affected.
5. Autonomic involvement is variable.
6. Tendon reflexes are LOST.
HSAN II - Affected genes:
1. Lysine-deficient protein kinase 1 (WNK1).
2. Family with sequence similarity 134, member B (FAM134B).
3. Kinesin family member 1A (KIF1A).
HSAN III (Riley-Day syndrome, familial dysautonomia):
2. Incr. prevalence in Ashkenazi Jews.
3. Onset in infancy.
4. Conspicuous autonomic dysfunction.
5. Absent taste sensation.
6. Impaired pain/temp sensation.
HSAN III (Riley-Day syndrome, familial dysautonomia) - Mutations:
Gene for inhibitor of kappa light polypeptide gene enhancer in B cells, kinase complex-associated protein (IKBKAP).
1. Congenital insensitivity to pain + absent sweating.
2. Many have cognitive dysfunction.
3. DEATH from hyperpyrexia may occur.
HSAN IV - Mutations:
AR mutations in the gene encoding a receptor tyrosine kinase for nerve growth factor (NTRK1).
Resembles HSAN IV, but NO CONGITIVE ABNORMALITIES.
HSAN V - Mutation:
Nerve growth factor beta-subunit gene (NGFB).
Hereditary neuropathy with liability to pressure palsies:
1. Genetically heterogenous disorder that relates most commonly to deletion in the peripheral myelin protein 22 (PMP22).
3. Patients present with simple/multiple mononeuropathies that occur after mild pressure or stretch of nerves.
4. Electrophysiologic studies reveal than abnormalities are more widespread than is evident clinically.
Metabolic disorders - AIP:
AR - The initial neurologic manifestation is often a polyneuropathy that usually involves MOTOR more than sensory fibers.
2 AR lipidoses are associated with polyneuropathy with a typical onset in infancy or childhood:
1. Metachromatic leukodystrophy --> Results from deficiency of the enzyme arylsulfatase A.
2. Krabbe disease --> Galactocerebroside beta-galactosidase deficiency.
Lipoprotein deficiencies that cause polyneuropathy include:
1. Abetalipoproteinemia (acanthocytosis, malabsorption, retinitis pigmentosa, and cerebellar ataxia).
2. Tangier disease (cataract, orange discoloration of tonsils, and hepatosplenomegaly).
--> BOTH AR.
AR --> Impaired metabolism of phytanic acid.
2. Cerebellar ataxia.
3. Retinitis pigmentosa.
X-linked recessive --> Alpha-galactosidase A deficiency.
1. PAINFUL sensory + autonomic neuropathy.
3. Renal/cardiac disease.
4. Incr. incidence of stroke.
Entrapment neuropathies - In many the initial or most conspicuous clinical complaints are of ...?
Sensory symptoms or pain.
Carpal tunnel syndrome - The diagnosis can be generally confirmed by ...?
Interdigital neuropathy - Such neuropathy may result from ...?
Entrapment in the intermetacarpal tunnel of the hand, direct trauma, tenosynovitis, or arthritis.
Thoracic outlet syndrome may simulate ...?
Carpal tunnel syndrome.
--> There may be diffuse weakness of the intrinsic hand muscles, often involving the thenar muscles.
Which nerve passes through the tarsal tunnel?
The posterior tibial nerve --> Can be compressed between the floor and the ligamentous roof of the tarsal tunnel --> Located in the ankle immediately below and behind the medial malleolus.
Isolated femoral neuropathy may occur in association with:
2. Vascular disease.
3. Bleeding diatheses (eg hemophilia or treatment with anticoagulant drugs).
4. Retroperitoneal neoplasms.
Meralgia paresthetica - Which nerve?
Lateral femoral cutaneous nerve.
Trauma to the obturator nerve - for example, by pelvic fracture or a surgical procedure - can lead to pain radiating from the groin down the inner aspect of the thigh.
Branchial plexopathy can result from ...?
Tumor infiltration, especially lung and breast, causing severe arm pain and sometimes dysesthesia.
--> LOWER trunk is MC involved --> C8-T1 dermatomes.
What should be suspected when the UPPER trunk of the branchial plexus is involved?
RADIATION injury, rather than direct invasion by tumor.
Lumbosacral plexopathy is usually seen in patients with ...?
Lyme disease - Peripheral nerve involvement:
1. Inflammatory mono- or poly-radiculopathy.
2. Branchial plexopathy.
3. Mononeuropathy (incl. facial palsy).
4. Mononeuropathy multiplex.
Syringomyelia is cavitation of the spinal cord. 2 types:
1. Communicating: Communication between the central canal of the cord and the cavity.
2. Non communicating: Cystic dilation of the cord, which is NOT in communication with the CSF pathways.
What is a common accompaniment of cord cavitation?
Cavitation that involves the lower brainstem:
Subacute combined degeneration - Clinical onset with ...?
Distal paresthesias and weakness in the extremities (early involvement of the hands).
--> Followed by the development of spastic paraparesis, with ataxia from impaired postural sensation in the legs.
Of which substance the abuse may lead to B12 def.?
Nitrous oxide abuse.
Which metal deficiency may cause subacute combined degeneration?
Peripheral nerve pain - Reflex sympathetic dystrophy:
General term --> Sympathetically mediated pain syndromes precipitated by a wide variety of tissue injuries, including soft tissue trauma, bone fractures, and myocardial infarction.
Which term is now used instead of reflex sympathetic dystrophy?
Complex regional pain syndrome (CRPS) type 1.
Pain that follows injury but spreads beyond the site of trauma in a distribution that does NOT conform to that of an individual peripheral nerve, is greater than would be expected from the injury, and may progress with time. (sometimes to the opposite limb).
CRPS I has been attributed to a ...?
Post-traumatic neuralgia associated with distal degeneration of SMALL-diameter peripheral axons.
Causalgia - Severe persistent pain, often burning in quality, that results from nerve trauma.
CRPS II - Features:
1. Onset: Any time within the first 6 weeks or so after the injury.
2. Cause: Uncertain, it has been attributed to ephaptic transmission between efferent sympathetic and afferent somatic fibers at the site of the injury.
Both types of CRPS may be accompanied by:
2. Incr. sweating.
4. Alodynia, hyperalgesia, muscle atrophy, and osteoporosis may also occur.