Diseases of the Peripheral Nerves Flashcards
3 distinct histopathologic changes in a peripheral nerve
segmental demyelination
wallerian degeneration
axonal degeneration
Focal degeneration of the myelin sheath with sparing of the axon
segmental demyelination
disappearance of the sheath over segments of variable length
“dying forward”
process in which the nerve degenerates from the point of axonal damage outward
Wallerian Degeneration
“dying back”
the axon is affected progressively from the distal-most site to the proximal
with dissolution of myelin that occurs roughly parallel with axonal change
Axonal Degeneration
which of the three cause muscle atrophy?
segmental demyelination
wallerian degeneration
axonal degeneration
wallerian and axonal degeneration
exception to the length-dependent pattern typical of axonal degeneration
porphyria - presents more of proximal weakness
Maximum degree of denervation atrophy after an acute injury to the axons occurs in _____ days and reduces _____% of muscle volume
90 to 120 days
75 to 80%
in GBS,
Other common antecedent events or associated illness include viral exanthems in children, bacterial infection
CMV EBV Campylobacter Mycoplasma pneumoniae Lyme diseases
define albuminocytologic dissociation
increase in protein without cells
Earliest change seen by Hafer-Macko and colleagues in the pathogenesis of GBS
deposition of complement on the inner layer of myelin
antibodies found in GBS patients with ophthalmoplegia
anti-GQ1b
antibodies found in GBS pts with predominantly motor presentation and to axonal damage
anti-GM1
high titers being associated with cases that follow Campylobacter infections
antibodies associated with pharyngeal-brachial-cervical variant of GBS
GD1a or GT1b
this neuropathy causes difficulty in weaning a patient from the ventilator even as the underlying critical illness comes under control
Critical illness Polyneuropathy
predominantly of motor type
sensory symptoms are mild
cranial nerves are spared
few or no dysautonomic symptoms
EMG/NCS and CSF finding in Critical Illness Polyneuropathy
in CIP: EMG NCS - primary axonal process with early denervation, normal CSF
vs demeylinative form of GBS
True or False
Differentiating Critical illness polyneuropathy from critical illness myopathy and from the axonal form of GBS is easy.
FALSE
Rapidly evolving sensory ataxia, areflexia, numbness and pain beginning in the face and spreading to involve the entire body
symptoms begain within 4 to 12 days following institution of penicillin therapy for a febrile illness
no weakness or muscle atrophy
NCV: absent or slowed sensory conduction, no abnormalities of motor nerve conduction and signs of denervation
Acute Sensory Neuronopathy
Acute Sensory Ganglionopathy
A polyneuropathy appearing 5-8 weeks later
acute or subacute limb weakness with paresthesias and distal loss of vibratory and position sense
weakness involves all extremities at the same time or may descend from arms to legs
may impair respiration
High protein in CSF 50-200mg/dL
Deaths that occur after the pharyngeal infection has subsided - cardiomyopathy; severe polyneuropathy then respiratory paralysis
segemental demyelination without inflammatory reaction of spina roots, ganglia, adjacent soinal nerves
anterior hornsm axons and muscle fibers remain normal.
Diphtheric Polyneuropathy
rapidly advancing, relapsing naturem acute onset more or less symmetrical and mainly motor polyneuropathy often with abdominal pain, psychosis (delirium or confusion) and convulsions
symptoms begin in feet and legs
weakness predominates in the proximal muscles of the limbs and limb girdle muscles, loss of knee jerks with preservation of ankle reflexes
porphyric polyneuropathy
autosomal dominant
not associated with cutaneoussensitivity to light
metabolic defect in Porphyric Polyneuropathy
metabolic defect is in the liver
marked by increased production and urinary excretion of porphobilinogen and of the porphyrin precursor
delta aminolevulinic acid
diagnosis in porphyric polyneuropathy
demonstration of large amounts or porphobilinogen and delta-aminolevulinic acid in urine
urine turns dark when standing as a consequence of the formation of porphobilin, oxidative product
Treatment in porphyric polyneuropathy
IV glucose and intravenous hematin 4mg/kg daily for 3 to 14 days
drugs implicated during recurrent attacks in porphyric polyneuropathy
sulfonamides, griseofulvin, estrogens, barbiturates, phenytoin,, succinimide anticonvulsant
Carcinoma of the _____ accounts for approximately 50% of the cases of paraneoplastic sensorimotor polyneuropathy
lung
True or False
Arsenical neuropathy is categorized as of the dying-back (axonal degeneration) type
True
Neuropathic symptoms develop slowly over a period of weeks or months
gastrointestinal symptoms may precede the polyneuropathy, associated with anemia, jaundice, brownish cutaneous pigmentation, hyperkeratosis of palms and soles, white transverse banding of the Nails (Mees lines)
Arsenical Polyneuropathy
it occurs following chronic exposure to paint or fumes (smelting industries or burning batteries)
from ingestion of liquor distilled in pipes
characteristic presnetation: motor mononeuropathy in the distribution of the radial nerves (wrist and finger drop)
may have sensory loss in radial territory of hand
foot-drop, less common
Lead Neuropathy
Plumbism
pathologic changes in lead neuropathy
axonal degeneration with secondayr myelin change and swelling and chromatolysis of anterior horn cells
lead accumulates in the nerve cells or to endothelial capillary cells causing edema
Associated medical findings in lead neuropathy/toxicity
anemia basophilic stippling or red blood cell precursors in bone marrow lead line along the gingival margins colicky abdomina pain constipation
Treatment in Lead toxicity/neuropathy
penicillamine generally safe and administered orally
preferable to dimercaprol and EDTA
antineoplastic drugs that can cause sensory polyneuropathy (5)
cisplatin
carboplatin
bortezomib
pacliatxel, docetaxel
antineoplastic agent most widely used in the tretament of lymphoma and leukemia
may cause some degree of weakness preceding sesory loss
extensors of fingers
dorsiflexors of toe and feet causing foot drop
vincristine
antimicrobial drug that causes symptoms of neuropathy
interferes with pyridoxine metabolism, by inhibiting the phosphorylation of pyridoxine and decreasing the tissue levels of its active form pyridoxal phosphate
isoniazid
treatment for isoniazid neuropathy
150 to 450 mg/day of pyridoxine
cardiac drug that may cause motor-sensory neuropathy
amiodarone
Clinical Syndromes of Diabetic Neuropathy
(1) the most common as noted is a distal, symmetrical, primarily sensory polyneuropathy affecting feet and legs in a chronic, slowly progressive manner; the others are
(2) acute ophthalmoplegia that affects the third, and less often the sixth, cranial nerve on one side;
(3) acute mononeuropathy of limbs or trunk including a painful thoracolumbar radiculopathy;
(4) an acute or subacute painful, asymmetrical, predominantly motor, multiple neuropathy affecting the upper lumbar roots and the proximal leg muscles (“diabetic amyotrophy”);
(5) a more symmetrical, proximal motor weakness and wasting, usually without pain and with variable sensory loss, pursuing a subacute or chronic course; and
(6) an autonomic neuropathy involving bowel, bladder, sweating and circulatory reflexes
in diabetic patients, isolated painful third nerve palsy with sparing of pupillary function
Diabetic Ophthalmoplegia
peripheral nerves most commonly affected in diabetic Mononeuropathy (3, FSP)
Femoral
Sciatic
Peroneal
recovery is the rule :)
in GBS
most frequent identifiable antecedent infection, but it accounts for only a relatively limited proportion of cases
Campylobacter jejuni
in GBS other common antecedent events or associated illness
cytomegalovirus [CMV],
Epstein-Barr virus [EBV],
HIV), and less often, bacterial infections other than Campylobacter (Mycoplasma pneumoniae, Lyme disease)
GBS
earliest immunologic event
complement deposition on myelin surface
earliest symptoms in GBs
paresthesias and numbness in toes and fingers
major clinical manifestation in GBS
weakness that evolves more or less symmetrically over a period of several days or a week or two
proximal and distal muscles are involved usually the lower extremities before the upper
Weakness progresses in approximately 5 percent of patients to total motor paralysis with respiratory failure within a few days. In severe cases, the ocular motor nerves are paralyzed and even the pupils may be unreactive.
True or False
In GBS.
More than half of the patients complain of pain and an aching discomfort in the muscles, mainly those of the hips, thighs, and back. These symptoms precede weakness and may be mistaken for lumbar disc disease, back strain, and orthopedic diseases.
true
in GBS
Urinary retention occurs in approximately ___ percent of patients soon after the onset of weakness, but catheterization is seldom required for more than a few days.
15%
Unlike the common form of demyelinating GBS, muscle atrophy became apparent relatively early in the _______ form (within weeks). The defining feature was the presence of numerous electrically inexcitable motor nerves and signs of extensive denervation.
axonal form
True or False
Most experience with the generalized axonal form of GBS indicates that recovery is good.
False
prolonged and incomplete.
GBS variant
Fisher syndrome
ataxia
areflexia
ophthalmoplegia
most important laboratory aids in GBS
electrodiagnostic exam and CSF examination
CSF in GBS
The protein content is usually normal during the first few days of illness, but then it rises, reaching a peak in ______ weeks and persisting at a variably elevated level for many weeks
4 to 6 weeks
frequent early diagnostic findings in GBS
reduction in the amplitude of muscle action potentials, slowed conduction velocity, and conduction block in motor nerves, singly or in combination
Prolonged distal latencies and reduced distal amplitudes (reflecting distal conduction block) and prolonged or absent F responses (indicating involvement of proximal parts of motor nerves and roots) all reflecting focal areas of demyelination
The H reflex is almost always much delayed
MRI of spinal cord in GBS
gadolinium enhancement of cauda equina
A rough estimate of breathing capacity may be obtained by having the patient count quickly on one deep breath. The ability to reach ______ generally corresponds to a vital capacity of greater than _____ L
20
1.5 L
oneiric hallucinations
bizarre waking dreams or hallucinations after weeks of immobilization
when to institute treatment in GBS
If the patient becomes unable to walk, shows a reduction in vital capacity, or signs of oropharyngeal weakness, plasma exchange or IVIg is instituted promptly
results of large randomized trials regarding plasma exchange in GBS
In patients who are treated within 2 weeks of onset, there is an approximate halving of the period of hospitalization, of the duration of mechanical ventilation, and of the time required to achieve independent ambulation.
However, in the largest trial, if the first plasma exchange was delayed for 2 weeks or longer after the onset of the disease, the procedure was of little value. Nonetheless, if a patient continues to progress in the third or fourth week of illness, it is probably still appropriate to institute the exchanges
most important predictors to responsiveness of GBS to plasma exchange
same with overall prognosis
patient’s age (responders are younger) and the preservation of motor compound muscle action potential amplitudes prior to instituting treatment
regimen for plasma exchange in GBS
advised regimen of plasma exchange removes a total of
200 to 250 mL/kg of plasma in 4 to 6 treatments on alternate days
IVIg regimen in GBS
0.4 g/kg per day for 5 days
infrequent complications of IVIg
renal failure
proteinuria
aseptic meningitis
mortality rate of GBS
3-5%
in GBS
The speed of recovery varies, but its pace is steady. Often, it occurs within a few weeks or months; however, if axons have been damaged, their regeneration may require ___ to ____months or longer
6 to 18 months
recurrence rate of acute polyneuropathy
5 to10 %
