内科学实习手册

1、内科学实习手册CAPTER 7: Neurology SystemSeizures and Epilepsy 4150A seizure is a paroxysmal eve nt due to abno rmal, excessive, hypers ynchronous discharges from an aggregate of cen tral n ervous system (CNS) neurons. Epilepsy describes a con diti on in which a pers on has recurre nt seizures due to a chro

2、nic, un derly ing process.1. Diag no sis1.1 Simple partial seizures Begin with motor, sensory, or autonomic phenomena, depe nding on the cortical regi on affected. Con scious ness is preserved. The abno rmal motor moveme nts may begi n in a very restricted regi on such as the fin gers, the face, a l

3、imb, or the pharynx. Focal seizure may spread from the distal part of the limb toward the ipsilateral face (jacks onian march). patie nts may experie nee a localized paresis (Todd's paralysis) for minutes to many hours in the involved region following the seizure. Autonomic symptoms may consist

4、of pallor, flushing, sweating, piloerection, pupillary dilatati on, vomit ing, borborygmi, and incontinen ce. Psychic symptoms in clude distorti ons of memory, forced thi nking or labored thought processes, cog nitive deficits, affective disturba nces (eg, fear, depressi on, an in appropriate sense

5、of pleasure), halluc in ati ons, or illusi ons.1.2 Complex partial seizures The symptoms are usually stereotyped. Episodes may beg in with an aura, epigastric sen sati ons are most com mon, but affective (fear),cognitive (d j 询)，and sensory (olfactory hallucinations) symptoms also occur.Con scious n

6、ess is the n impaired. Seizures gen erally persist for less tha n 30 mi nu tes (on the average, 1 minu tes). The motor mani festati ons are characterized by automatism, such as orobuccoli ngual moveme nts and other facial or n eck moveme nts.1.3 Abse nee seizures (petit mal) Are characterized by sud

7、de n, brief loss of con scious ness without loss of postural con trol. The seizure typically lasts for on ly sec on ds, con scious ness returns as sudde nly as it was lost, and there is no postictal con fusi on. Abse nee seizures are usually accompa nied by subtle, bilateral motor sig ns such as rap

8、id bli nking , chew ing moveme nts, or small-amplitude, clonic moveme nts of the han ds. Abse nee seizures usually begi n in childhood (ages 4 to 8) or early adolesce nee. The seizures can occur hun dreds of times per day.1.4 Gen eralized toni c-cl onic seizures (gra nd mal)Begi n abruptly without w

9、arning. The initial phase is usually tonic contraction of muscles throughout the body, tonic eon tract ion of the muscles of expirati on and the lary nx will produce a loud moan or “ ictal cry ” . Respirations are impaired, and eyanopis. Patients may bite their ton gue. A marked enhan ceme nt of sym

10、pathetic tone leads to in creases in heart rate, blood pressure, and pupillary size. After 10 to 20 s, the tonic phase typically evolves into the clonic phase. The periods of relaxati on progressively in crease un til the end of the ictal phase, which usually lasts no more than 1 min. Bladder or bow

11、el incon ti nenee may occur. Patie nts gradually rega in eon scious ness over minu tes to hours. There is typically a postictal eon fusi on, headache, fatigue, and muscle ache.1.5 Lab Studies Routine blood studies are indicated to identify the abnormalities in electrolytes, glucose, calcium, or magn

12、 esium, and hepatic or renal disease. A lumbar puncture is indicated if there is any suspicion of meningitis or encephalitis.1.6 Electroe ncephalographyEpileptiform discharges (spikes and sharp waves) arehighly correlated with seizure susceptibility. However, 10% to 40% of patie nts with epilepsy do

13、 not show epileptiform abnormalities on routine EEG. Sleep, hyperve ntilati on, photic stimulati on, and special electrode placeme nts are routi nely used to in crease the probability of recordi ng epileptiform abno rmalities.1.7 Imagi ng studies Almost all patie nts with n ew-on set seizures should

14、 accept MRI or CT to detect cerebral lesions associated with epilepsy, such as tumors, vascular malformations, or other pathologies.2. Differe ntial Diag no sis2.1 Syn cope Characteristics of a seizure in clude the prese nee of cyano sis, unconsciousness, motor manifestations lasting >30 s, posti

15、ctal disorientation, drowsy and muscle sore ness. In con trast, a syn copal episode is more likely was provoked by acute pain or anxiety or occurred immediately after arising from the lying or sitting position. A stereotyped transition from consciousness to unconsciousness that includes tiredness, s

16、weating, nausea, and tunneling of vision often be described. Patients experience a relatively brief loss of consciousness.2.2 Pseudoseizures In patients with pseudoseizures resembling tonic-clonic attacks, there may be warning and preparation before the attack, there is usually no tonic phase, and t

17、he clonic phase con sists of wild thrash ing moveme nts duri ng which the patient rarely comes to harm or is incontinent. There is no postictal confusion or abno rmal cli nical sig ns followi ng the attack. The EEG recorded duri ng the episode does not show seizure activity, and postictal slowing do

18、es not occur.3. Treatme nt3.1 Medical treatme nt3.1.1 Therapy of epilepsy has three goals: To eliminate seizures or reduce their freque ncy to the maximum exte nt possible, to avoid the side effects associated with Iong-term treatment, and to assist the patient in maintaining or restoring normal psy

19、chosocial and vocati onal adjustme nt.3.1.2 Selection of antiepileptic drugsDrugs are chosen based on the seizure type. Valproate is the drug of choice for gen eralized-on setseizures. Lamotrig ine and probably topiramate are alter natives if valproate is in effective or not tolerated. Phe nytoin an

20、d carbamazep ine are also effective against generalized tonic-clonic seizure, both are drugs of first choice for partial and sec on darily gen eralized seizures. For sec on darily gen eralized seizures, valproate is also effective. Lamotrig ine is comparable in effective ness with phe nytoin and car

21、bamazep ine and that gabape ntin shows similar efficacy to carbamazep ine for treatme nt of n ew-on set partial seizures. Carbamazep in e,phe nytoin, gabape nti n, and sometimes lamotrigine can aggravate myoclonic seizures. All of these except lamotrigi ne also sometimes exacerbate abse nce seizures

22、. Tiagab ine can aggravate or induce absence seizures. Ethosuximide is as effective as valproate in controlling abse nce seizures.3.2 Surgical treatme ntSurgery should be con sidered when seizures are uncon trolled by optimal medical management and when they disrupt the quality of life. Anterior tem

23、poral lobe resect ion, lesi on ectomy, nonl esi onal cortical resect ions, corpus callosotomy or hemispherectomy could be selected.Parki nson Disease 4650Park inson's disease (PD) is a n eurodege nerative disorders characterized by resti ng tremor, rigidity, bradyk in esia and postural in stabil

24、ity. The average age of on set is approximately 60 years.1. Diag no sis1.1 Cli nical fin di ngs1.1.1 Resti ng-tremor The 4- to 6-Hz pill-rolli ng like tremor is most con spicuous at rest, it in creases at times of emoti onal stress and ofte n improves duri ng volun tary activity. It com monly beg in

25、s in the hand or foot, may ultimately be prese nt in all of the limbs.1.1.2 Rigidity Is a in creased resista nee to passive moveme nt. The resista nee is typically uniform throughout the range of movement (lead-pipe rigidity ). In somein sta nces, the rigidity is described as cogwheel rigidity becau

26、se of the superimposed tremor.1.1.3 Bradykinesia The patient's face is relatively immobile (masklike facies), with wide ned palpebral fissures, in freque nt bli nking. The voice is of low volume (hypophonia). Fine or rapidly alternating movements are impaired. The handwriting is small.1.1.4 Abno

27、 rmal gait and posture It is difficult to get up from bed and tends to adopt a flexed posture on standing, and it is often difficult to start walking. The gait itself is characterized by small, shuffling steps and absence of the arm swing. There is gen erally some un stead in ess on tur ning, and th

28、ere may be difficulty in stopp ing. In adva need cases, the patie nt tends to walk with in creas ing speed to preve nt a fall (fest in ati ng gait).1.1.5 Other cli nical featuresThere is ofte n mild blepharocl onus and occasi on allyblepharospasm. The patie nt may drool because of impairme nt of swa

29、llow ing. Repetitive tapping over the bridge of the nose produces a sustained blink response (Myers on sig n). Cogn itive decli ne sometimes occurs but is usually mild and late, depression and visual hallucinations are frequent. Urinary urgency, urge incontinence, con stipati on and postural hypote

30、nsion are com mon.1.2 Lab studies No laboratory biomarkers exist for PD. Serum ceruloplasm in concen trati on is obta ined as a scree ning test for Wils on disease.1.3 Imaging studies MRI and CT are unremarkable in PD.2 Differential Diagnosis2.1 Essential temor(ET) The absence of other signs of park

31、insonism and the bilaterality, higher frequency (8 to 10 Hz), and postural dependency of ET plus significant relief with even a small amount of alcohol help differentiate this from the rest tremor of PD.2.2 Dementia with Lewy bodies It is characterized by a rapidly progressing dementia, hallucinatio

32、ns and extrapyramidal motor features. There is only an incomplete response to levodopa, but patients are extremely sensitive to parkinsonian complications of neuroleptics.2.3 Wilson disease The early age at onset and the presence of Kayser-Fleischer rings should distinguish Wilson disease from Parki

33、nson disease, as should the abnormalities in serum and urinary copper and serum ceruloplasmin that occur in Wilson disease.3 Treatment3.1 Anticholinergic drugs These agents provide benefit for tremor in approximately 50% of patients, but do not improve bradykinesia or rigidity. Common side effects i

34、nclude dryness of the mouth, constipation, urinary retention, and defective pupillary accommodation. Confusion, especially in the elderly, is due to antimuscarinic effects in the brain. Artane: 1-2 mg/d, three times a day, increase by 2 mg/d at intervals of 3-5 d, young adults may tolerate 15-20 mg/

35、d divided tid/qid, older individuals may tolerate no more than 4-8 mg/d.3.2 Amantadine Amantadine can be given for mild parkinsonism either alone or in combination with an anticholinergic agent. it improves all the clinical features of parkinsonism, its side effects include restlessness, confusion,

36、skin rashes, edema, disturbances of cardiac rhythm, and it is given in a standard dose of 100 mg orally twice daily.3.3 Levodopa Levodopa/PDI (peripheral decarboxylase inhibitor) is the criterion standard of symptomatic treatment for PD. Patients should receive lowest dose that provides good control

37、 of parkinsonian symptoms. Madopar(L-Dopa + benserazide) is given initially 62.5mg 2 to 3 times daily, increasing to 250mg three times orally daily. Long-term treatment with levodopa results in the development of motor complications, reduced duration of antiparkinsonian action (wearing off phenomeno

38、n), sudden shifts between under-treated and over-treated states (on-off phenomenon).3.4 Dopamine agonists Piribedil and pramipexole are effective as monotherapy in early PD and as adjuncts to levodopa/PDI in moderate to advanced disease. After 6 mon ths to a few years, they are not as effective as l

39、evodopa/PDI. The additi on of a dopam ine ago nist reduces off time, improves motor function, and allows lower levodopa doses. Adverse effects of these medicatio ns in clude fatigue, somnolen ce, nausea, peripheral edema, dyskinesias, confusion, hallucinations, orthostatic hypote nsion and an irresi

40、stible urge to sleep.3.5 Mon oami ne oxidase B (MAO-B) in hibitorsIn hibit the activity of MAO-B thatis resp on sible for in activati ng dopam ine and possibly the conv ersi on of compo unds into neurotoxic types. Selegiline: 2.5-5 mg, twice daily with breakfast and lunch; not to exceed 10 mg/d.3.6

41、Catechol-O-methyltra nsferase(COMT) In hibitors For patie nts with motor fluctuati ons on levodopa/carbidopa, the additi on of a COMT in hibitor decreases off time, improves motor fun cti on, and allows lower levodopa doses. En tacap one (200 mg) take n with sin emet up to five times daily is gen er

42、ally preferred.3.7 Surgery Thalamotomy or pallidotomy is ofte n helpful whe n patie nts becomeun resp on sive to pharmacologic measures or develop in tolerable adverse react ions to an tipark insonian medicati on. Thalamotomy is more helpful for tremor, and pallidotomy for hypok in esia.3.8 Deep bra

43、in stimulatio n( DBS)DBS of the globus pallidus or subthalamicnu cleus may help all the card inal features of the disease and reduces the time spe nt in the off-state in patients with fluctuations.3.9 Protective therapy MAO-B in hibitors such as selegili ne and rasagili ne have an ti-apoptotic prope

44、rties, as also do certa in dopam ine agoni sts.Myasthe nia Gravis 4900Myasthe nia gravis (MG) is an acquired autoim mune disorder characterized cli ni cally by weak ness of skeletal muscles and fatigability on exerti on. The autoa ntibodies against acetylcholine receptors(AchR) in the neuromuscular

45、junction (NMJ) are resp on sible for the MG.1. Diag no sis1.1 Cli nical characteristic1.1.1 The peak age of on set is betwee n 20 and 30 years in wome n and betwee n 50 and 60 years in men. The cardinal features are weakness and fatigability of muscles. The weak ness in creases duri ng repeated use

46、and may improve follow ing rest.1.1.2 Extraocular muscle (EOM) weakness or ptosis is present initially in 50% of patients and occurs during the course of illness in 90% of patients.1.1.3 Weakness tends to spread from the ocular to facial, bulbar, then to truncal and limb muscles. Facial weakness pro

47、duces “a snarling ” expression when the patient attempts to smile, weakness of masseter is most noticeable in chewing meat, speech may have a nasal timbre. Difficulty in swallowing may give rise to nasal regurgitation or aspiration of liquids or food. The limb weakness in MG is often proximal and ma

48、y be asymmetric. Deep tendon reflexes are preserved.1.1.4 In patients with generalized disease, the interval from onset to maximal weakness is less than 36 months in 83% of patients.1.2 Laboratory studies1.2.1 Anti-AchR antibody The anti-AChR antibody is positive in 74% of patients. The anti-AChR Ab

49、 test result is frequently negative in patients with only ocular MG.1.2.2 Antistriated muscle (anti-SM) Ab It is present in about 84% of patients with thymoma who are younger than 40 years and less often in patients without thymoma, its presence should prompt a search for thymoma in patients younger

50、 than 40 years. In individuals older than 40 years, anti-SM Ab can be present without thymoma.1.2.3 Thyroid function It should be carried out routinely in patients with suspected MG. Abnormalities of thyroid function (hyper- or hypothyroidism) may increase myasthenic weakness.1.3 Imaging studies1.3.

51、1 Chest radiograph and CT Plain anteroposterior and lateral views may identify a thymoma as an anterior mediastinal mass, a negative chest radiograph does not rule out a smaller thymoma, in which case a chest CT scan is required.1.3.2 Pharmacological testing1.3.2.1 Edrophonium (Tensilon) test Edroph

52、onium is given intravenously in a dose of 10 mg (1 mL), of which 2 mg is given initially and the remaining 8 mg about 30 seconds later if the test dose is well tolerated. In myasthenic patients, there is an obvious improvement in the strength of weak muscles that lasts for about 5 minutes.1.3.2.2 Ne

53、ostigmine tests Neostigmine methylsulfate is injected intramuscularly in a dose of 1.5 mg, atropine sulfate (0.5 mg) should be given several minutes in advance to counteract muscarinic effects. After intramuscular injection, objective and subjective improvement occurs within 10 to 15 min, reaches it

54、s peak at 20 min, and lasts up to 1 h.1.3.4 Electromyography1.3.4.1 Repetitive nerve stimulation (RNS) RNS induces a rapid reduction in the amplitude of the evoked responses.1.3.4.2 Single-fiber electromyography (SFEMG) SFEMG shows increased variability in the interval between two muscle fiber actio

55、n potentials from the same motor unit in clinically weak muscles.2. Differential Diagnosis2.1 Lambert-Eaton myasthenic syndrome (LEMS)LEMS is a presynapticdisorder caused by autoantibodies directed against P/Q type calcium channels at the motor nerve terminals, which may signal the presence of the t

56、umor long before it would be detected. The proximal muscles of the lower limbs are most commonly affected. Patients with LEMS have depressed or absent reflexes, show autonomic changes such as dry mouth and impotence. Incremental rather than decremental responses is found on RNS. A majority of patien

57、ts with this syndrome have an associated malignancy, most commonly small-cell carcinoma of the lung.2.2 Botulism The pupils are often dilated, the eyesigns are followed rapidly by involvement of bulbar, trunk, and limb muscles. Repetitive nerve stimulation gives an incremental response.3 Treatment3.

58、1 Anticholinesterase (AChE)inhibitorThese agents inhibit AChE, raising theconcentration of ACh at the NMJ and increasing the chance of activating the AChR. Pyridostigmine bromide are considered to be the basic treatment of MG, the usual dose of pyridostigmine is 30 to 90 mg given every 6 h.3.2 Immun

59、omodulatory therapyThe patients with generalized MG requireadditional immunomodulating therapy. Immunomodulation can be achieved by corticosteroids , azathioprine, cyclosporine, cyclophosphamide, and rituximab. Prednisone is administrated with starting dose of 20 mg/d, increasing by 10 mg per week until satisfactory clinical response achieved or maximum dose of 60-80 mg/d reached, taper should begin after 3-6 months of treatment and d