IUHS Student-2-Student USMLE Step 1 Recall
Central Nervous System
Peripheral Nerve
Guillain-Barre Syndrome
it is one of the most common life-threatening diseases of the PNS with an overall annual incidence of 1 to 3 cases per 100,000 persons in the US...
the disease is characterized clinically by weakness beginning in the distal limbs but rapidly advancing to affect more proximal muscle functions (ascending paralysis) and histologically by inflammation and demyelination of peripheral nerves and spinal nerve roots (radiculoneuropathy)...
a respiratory infection almost always preceeds Guillain Barre Syndrome...
approximately two thirds of cases are preceded by an acute, influenza-like illness, usually viral, from which the patient has recovered by the time the neuropathy becomes symptomatic...
there has been no consistent demonstration of any infectious agent in peripheral nerves in these patients, and an immunologically mediated disorder is now generally favored...
a similar inflammatory disease of peripheral nerves can be induced in experimental animals by sensitization to peripheral nerve myelin or its components...
a T cell mediated immune response ensues, accompanied by segmental demyelination effected by macrophages...
transfer of these T cells to a naive animal results in comparable lesions...
moreover, lymphocytes from patients with Guillain-Barre syndrome have been shown to produce demyelination in tissue cultures of myelinated nerve fibers...
circulating antibodies may also play a part, and plasmapheresis has been reported to be an effective treatment...
the dominant histopathologic finding is inflammation of peripheral nerve, manifested as perivenular and endoneurial infiltration by lymphocytes, macrophages, and a few plasma cells...
the invading inflammatory cells vary in number from a sparse seeding of the perivenous spaces to large collections of mononuclear cells disseminated througout the entire nerve...
segmental demyelination affecting peripheral nerves is the primary lesion, but damage to axons is also characteristic, particularly when the disease is severe...
electron microscopy has identified an early effect on myelin sheaths...the cytoplasmic processes of macrophages penetrate the basement membrane of schwann cells, particularly in the vicinity of the nodes of ranvier, and extend between the mylein lamellae, stripping away the myelin sheath from the axon...
ultimately, the remnants of the mylein sheath are engulfed by the macrophages...remyelinaiton follows the demyelination...
inflammatory foci and demyelination are widely distributed throughout the PNS, although their intensity is so variable that they may be difficult to identify in an individual case...the most intense inflammatory reaction is often localized in spinal and cranial motor roots and the adjacent parts of the spinal and cranial nerves...
the clinical picture is dominated by the ascending paralysis...
deep tendon reflexes disappear early in the process; although sensory involvement can often be dectected, it is less troublesome than the weakness...
the nerve conduction velocity is slowed b/c of the multifocal destruction of myelin segments involving many axons within a nerve; there is elevation of the CSF protein due to inflammation and altered permeability of the microcirculation within the spinal roots as they traverse the subarachnoid space...
inflammatory cells are contained within the roots, however, there is little to no CSF pleocytosis...
many patients spend weeks in hospital intensive care units before recovering normal function...
with improved respiratory care and support, the mortality rate has fallen from 25% in the past but is still considerable, with some 2-5% dying of respiratory paralysis, autonomic instability, and the complications of tracheostomy...
Myotonic Dystrophy
myotonia, the sustained involuntary contraction of a group of muscles, is the cardinal neuromuscular symptom in this disease...
patients often complain of "stiffness" and have difficulty in releasing their grip, like after a handshake...
myotonia can often be elicited by percussion of the thenar eminence...
inherited as an autosomal dominant trait, the disease tend to increase in severity and appear at a younger age in succeeding generations, a phenomenon termed anticipation...
the gene for myotonic dystrophy, localized to 19q13.2-13.3 encodes a protein kinase termed myotonin protein kinase...
located in the 3' untranslated region of the gene, it is a trinucleotide repeat, consisting of CTG...
the disease phenotype is associated with expansion of thisa region: in normal subjects fewer than 30 repeats are present; in severly affected individuals, several thousand may be present...
the
mutation is not stable within a pedigree; with each generation, more repeats
accumulate, and this appears to correspond to the clinical feature of
anticipation...
expansion of the trinucleotide repeat influences the eventual level of protein product...
the disease often presents in late childhood with abnormalities in gait secondary to weakness of foot dorsiflexors and subsequently progresses to weakness of the hand intrinsic muscles and wrist extensors...
atrophy of muscles of the face and ptosis ensues, leading to the typical facial appearance...
cataracts, which are present in virtually every patient, may be detected early in the course of the disease with slit-lamp examination...
other associated abnormalities include frontal balding, gonadal atrophy, cardiomyopathy, smooth muscle involvement, decreased plasma immunoglobulin G, and an abnormal glucose tolerance test response...
dementia has been reported in some cases....
the disease may present as congenital weakness and is then associated with maternal inheritance...
in these cases, symptoms are severe, with facial muscle weakness (diplegia), feeding difficulties, and respiratory insufficiency...
Myasthenia Gravis
myasthenia gravis is a muscle disease caused by immune mediated loss of acetylcholine receptors and having characteristic temporal and anatomic patterns as well as drug responses...
the disease has a prevalence of about 3 in 100,000 persons...
when arising before age 40 years, it is most commonly seen in women, but there is equal occurrence between the sexes in older patients...
thymic hyperplasia is found in 65% and thymoma in 15% of patients...
analysis of neuromuscular transmission in myasthenia gravis shows a decrease in the number of muscle acetylcholine receptors (AChRs), and circulating antibodies to the AChR are present in nearly all patients with myasthenia gravis...
the disease can be passively transferred to animals with serum from affected patients...
the circulating anti-AChR antibodies apparently increase the degradation rate of the AChR, leading to a decreased receptor number, and also apppear to fix complement and lead to direct injury to the postsynaptic membrane...
despite
the evidence that these antibodies play a critical pathogenic role in the
disease, there is not always a correlation beween antibody levels and neurologic
deficit...
interestingly, in light of the immune mediated etiology of the disease, thymic abnormalities are common in these patients, but the precise link for autoimmunity to AChRs is uncertain...
regardless of the pattern of thymic pathology, most patients show improvement after thymectomy...
typically, weakness begins with extraocular muscles; drooping eyelids (ptosis) and double vision (diplopia) cause the patient to seek medical attention...
however, the initial symptoms may include generalized weakness...the weakness fluctuates, with alteration occurring during days, hours, or even minutes, and intercurrent medical conditions can lead to exacerbation of the weakness...
patients show improvement in strength in response to administration of anticholinesterase agents...
this remains a most usuful test on clinical examination...
respiratory compromise was a major cause of mortality in the past; 95% of patients survive after 5 years b/c of improved methods of tretment and better ventilatory support...
effective forms of treatment include anticholinesterase drugs, prednisone, plasmapheresis, and resection of thymoma if it is present...
antiacetylcholine receptor radioimmunoassay, if positive, will definitively diagnosis MG....
Lambert-Eaton Myasthenic Syndrome
antibodies to the release of of acetylcholine, whereas MG has antibodies to the acetylcholine receptors...
lambert-eaton myasthenic syndrome is a disease of the neuromuscular junction that is distinct from myasthenia gravis...
it usually develops as a paraneoplastic process, most commonly with small cell carcinoma of the lung (60% of cases) although it can occur in the absence of underlying malignant disease...
patients develop proximal muscle weakness along with autonomic dysfunction...
no clinical improvement is found with the tensilon test, and electrophysiologic studies show evidence of enhanced neurotransmission with repetitive stimulation...
these clinical features allow this disorder to be distinguished from myasthenia gravis...
the content of anticholinesterase is normal in neuromuscular junction synaptic vesicles, and the postsynaptic membrane is normally responsibe to anticholinesterase, but fewer vesicles are released in response to each presynaptic action potential...
some patients have antibodies that recognize presynaptic calcium channels, and a similar disease can be transferred to animals with these antibodies...
this suggests that autoimmunity to the calcium channel causes the disease...