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CAPTER 7: Neurology System

Seizures and Epilepsy 4150

A seizure is a paroxysmal event due to abnormal, excessive, hypersynchronous discharges from an aggregate of central nervous system (CNS) neurons. Epilepsy describes a condition in which a person has recurrent seizures due to a chronic, underlying process.

1. Diagnosis

1.1 Simple partial seizures Begin with motor, sensory, or autonomic phenomena, depending on the cortical region affected. Consciousness is

preserved. The abnormal motor movements may begin in a very restricted region such as the fingers, the face, a limb, or the pharynx. Focal seizure may spread from the distal part of the limb toward the ipsilateral face (jacksonian march). patients may experience a localized paresis (Todd's paralysis) for minutes to many hours in the involved region following the seizure. Autonomic symptoms may consist of pallor, flushing, sweating, piloerection, pupillary dilatation, vomiting, borborygmi, and incontinence. Psychic symptoms include distortions of memory, forced thinking or labored thought processes, cognitive deficits, affective disturbances (eg, fear, depression, an inappropriate sense of pleasure), hallucinations, or illusions.

1.2 Complex partial seizures The symptoms are usually stereotyped. Episodes may begin with an aura, epigastric sensations are most common, but affective (fear), cognitive (déjà vu), and sensory (olfactory hallucinations) symptoms also occur. Consciousness is then impaired. Seizures generally persist for less than 30 minutes (on the average, 1–3 minutes). The motor manifestations are characterized by automatism, such as orobuccolingual movements and other facial or neck movements.

1.3 Absence seizures (petit mal) Are characterized by sudden, brief loss of consciousness without loss of postural control. The seizure typically lasts for only seconds, consciousness returns as suddenly as it was lost, and there is no postictal confusion. Absence seizures are usually accompanied by subtle, bilateral motor signs such as rapid blinking , chewing movements, or small-amplitude, clonic movements of the hands. Absence seizures usually begin in childhood (ages 4 to 8) or early adolescence. The seizures can occur hundreds of times per day.

1.4 Generalized tonic-clonic seizures (grand mal) Begin abruptly without warning. The initial phase is usually tonic contraction of muscles throughout the body, tonic contraction of the muscles of expiration and the larynx will produce a loud moan or “ictal cry”. Respirations are impaired, and cyanosis develops. Patients may bite their tongue. A marked enhancement of sympathetic tone leads to increases 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 relaxation progressively increase until the end of the ictal phase, which usually lasts no more than 1 min. Bladder or bowel incontinence may occur. Patients gradually regain

consciousness over minutes to hours. There is typically a postictal confusion, headache, fatigue, and muscle ache.

1.5 Lab Studies Routine blood studies are indicated to identify the

abnormalities in electrolytes, glucose, calcium, or magnesium, and hepatic or renal disease. A lumbar puncture is indicated if there is any suspicion of meningitis or encephalitis.

1.6 Electroencephalography Epileptiform discharges (spikes and sharp waves) are highly correlated with seizure susceptibility. However, 10% to 40% of patients with epilepsy do not show epileptiform abnormalities on routine EEG. Sleep, hyperventilation, photic stimulation, and special electrode placements are routinely used to increase the probability of recording epileptiform abnormalities.

1.7 Imaging studies Almost all patients with new-onset seizures should accept MRI or CT to detect cerebral lesions associated with epilepsy, such as tumors, vascular malformations, or other pathologies.

2.Differential Diagnosis

2.1 Syncope Characteristics of a seizure include the presence of cyanosis, unconsciousness, motor manifestations lasting >30 s, postictal disorientation, drowsy and muscle soreness. In contrast, a syncopal 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, sweating, 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 the clonic phase consists of wild thrashing movements during which the patient rarely comes to harm or is incontinent. There is no postictal confusion or abnormal clinical signs following the attack. The EEG recorded during the episode does not show seizure activity, and postictal slowing does not occur.

3. Treatment

3.1 Medical treatment

3.1.1 Therapy of epilepsy has three goals: To eliminate seizures or reduce their frequency to the maximum extent possible, to avoid the side effects associated with long-term treatment, and to assist the patient in maintaining or restoring normal psychosocial and vocational adjustment.

3.1.2 Selection of antiepileptic drugs

Drugs are chosen based on the seizure type. Valproate is the drug of choice for generalized-onset seizures. Lamotrigine and probably topiramate are alternatives if valproate is ineffective or not tolerated. Phenytoin and carbamazepine are also effective against generalized tonic-clonic seizure, both are drugs of first choice for

partial and secondarily generalized seizures. For secondarily generalized seizures, valproate is also effective. Lamotrigine is comparable in effectiveness with phenytoin and carbamazepine and that gabapentin shows similar efficacy to carbamazepine for treatment of new-onset partial seizures. Carbamazepine, phenytoin, gabapentin, and sometimes lamotrigine can aggravate myoclonic seizures. All of these except lamotrigine also sometimes exacerbate absence seizures. Tiagabine can aggravate or induce absence seizures. Ethosuximide is as effective as valproate in controlling absence seizures.

3.2 Surgical treatment

Surgery should be considered when seizures are uncontrolled by optimal medical management and when they disrupt the quality of life. Anterior temporal lobe resection, lesionectomy, nonlesional cortical resections, corpus callosotomy or hemispherectomy could be selected.

Parkinson Disease 4650

Parkinson's disease (PD) is a neurodegenerative disorders characterized by resting tremor, rigidity, bradykinesia and postural instability. The average age of onset is approximately 60 years.

1. Diagnosis

1.1 Clinical findings

1.1.1 Resting-tremor The 4- to 6-Hz pill-rolling like tremor is most conspicuous at rest, it increases at times of emotional stress and often improves during voluntary activity. It commonly begins in the hand or foot, may ultimately be present in all of the limbs.

1.1.2 Rigidity Is a increased resistance to passive movement. The resistance is typically uniform throughout the range of movement (lead-pipe rigidity ). In some instances, the rigidity is described as cogwheel rigidity because of the superimposed tremor.

1.1.3 Bradykinesia The patient's face is relatively immobile (masklike facies), with widened palpebral fissures, infrequent blinking. The voice is of low volume (hypophonia). Fine or rapidly alternating movements are impaired. The handwriting is small.

1.1.4 Abnormal 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 generally some unsteadiness on turning, and there may be difficulty in stopping. In advanced cases, the patient tends to walk with increasing speed to prevent a fall (festinating gait).

1.1.5 Other clinical features There is often mild blepharoclonus and occasionally blepharospasm. The patient may drool because of impairment of swallowing. Repetitive tapping over the bridge of the nose produces a sustained

blink response (Myerson sign). Cognitive decline sometimes occurs but is usually mild and late, depression and visual hallucinations are frequent. Urinary urgency, urge incontinence, constipation and postural hypotension are common.

1.2 Lab studies No laboratory biomarkers exist for PD. Serum ceruloplasmin concentration is obtained as a screening test for Wilson disease.

1.3 Imaging studies MRI and CT are unremarkable in PD.

2 Differential Diagnosis

2.1 Essential temor(ET) The absence of other signs of parkinsonism 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, hallucinations 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 Parkinson disease, as should the abnormalities in serum and urinary copper and serum ceruloplasmin that occur in Wilson disease.

3 Treatment

3.1 Anticholinergic drugs These agents provide benefit for tremor in approximately 50% of patients, but do not improve bradykinesia or rigidity. Common side effects include 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/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, 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 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 phenomenon), 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 months to a few years, they are not as effective as levodopa/PDI. The addition of a dopamine agonist reduces off time, improves motor function, and allows lower levodopa doses. Adverse effects of these medications include fatigue, somnolence, nausea, peripheral edema, dyskinesias, confusion, hallucinations, orthostatic hypotension and an irresistible urge to sleep.

3.5 Monoamine oxidase B (MAO-B) inhibitors Inhibit the activity of MAO-B that is responsible for inactivating dopamine and possibly the conversion of compounds into neurotoxic types. Selegiline: 2.5-5 mg, twice daily with breakfast and lunch; not to exceed 10 mg/d.

3.6 Catechol-O-methyltransferase(COMT) Inhibitors For patients with motor fluctuations on levodopa/carbidopa, the addition of a COMT inhibitor decreases off time, improves motor function, and allows lower levodopa doses. Entacapone (200 mg) taken with sinemet up to five times daily is generally preferred.

3.7 Surgery Thalamotomy or pallidotomy is often helpful when patients become unresponsive to pharmacologic measures or develop intolerable adverse reactions to antiparkinsonian medication. Thalamotomy is more helpful for tremor, and pallidotomy for hypokinesia.

3.8 Deep brain stimulation(DBS) DBS of the globus pallidus or subthalamic

nucleus may help all the cardinal features of the disease and reduces the time spent in the off-state in patients with fluctuations.

3.9 Protective therapy MAO-B inhibitors such as selegiline and rasagiline have anti-apoptotic properties, as also do certain dopamine agonists.

Myasthenia Gravis 4900

Myasthenia gravis (MG) is an acquired autoimmune disorder characterized clinically by weakness of skeletal muscles and fatigability on exertion. The autoantibodies against acetylcholine receptors(AchR) in the neuromuscular junction (NMJ) are responsible for the MG.

1.Diagnosis

1.1 Clinical characteristic

1.1.1 The peak age of onset is between 20 and 30 years in women and between 50 and 60 years in men. The cardinal features are weakness and fatigability of muscles. The weakness increases during repeated use and may improve following 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 produces 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 may 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 studies

1.2.1 Anti-AchR antibody The anti-AChR antibody is positive in 74% of patients. The anti-AChR Ab 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 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 studies

1.3.1 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 testing

1.3.2.1 Edrophonium (Tensilon) test Edrophonium 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 Neostigmine 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 its peak at 20 min, and lasts up to 1 h.

1.3.4 Electromyography

1.3.4.1 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 action potentials from the same motor unit in clinically weak muscles.

2. Differential Diagnosis

2.1 Lambert-Eaton myasthenic syndrome (LEMS) LEMS is a presynaptic disorder caused by autoantibodies directed against P/Q type calcium channels at the motor nerve terminals, which may signal the presence of the tumor 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 patients 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 Treatment

3.1 Anticholinesterase (AChE)inhibitor These agents inhibit AChE, raising the concentration 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 Immunomodulatory therapy The patients with generalized MG require additional 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 documented response.

3.3 Plasma exchange (PE) PE is an effective treatment for MG, especially in preparation for surgery or as short-term management of an exacerbation. Weakness improves within days, but the improvement lasts only 6-8 weeks.

3.4 Surgical care This is an important treatment option in MG, especially if a thymoma is present. Thymectomy may induce remission. This occurs more frequently in young patients with a short duration of disease, hyperplastic thymus, and high antibody titer.

3.5 Treatment of myasthenic crisis Timely intubation followed by mechanical ventilation is mandatory. The possibility of cholinergic crisis is best excluded by temporarily stopping the anticholinesterase drugs. The underlying infection should be treated immediately. The use of PE appears to hasten improvement and weaning from the ventilator. Intravenous gamma globulin may be a useful alternative. Use high-dose corticosteroid infusions, in the short run, carries the risk of inducing worsening of the weakness.

Hypokalemic periodic paralysis 3200

Hypokalemic periodic paralysis is a rare, autosomal dominant channelopathy characterized by muscle weakness or paralysis with a matching fall in potassium levels in the blood, primarily due to defect in a voltage-gated calcium channel.

1. Diagnosis

1.1 Symptoms and signs

1.1.1 It apparent between 10 and 20 years of age and may remit after 35 years of age. Attacks often develope after a heavy carbohydrate meal or a period of rest following prolonged exercise. It commonly occurs during the night or is present on waking in the morning.

1.1.2 The extent of the paralysis varies from slight weakness of the legs to complete paralysis of all the muscles of the trunk and limbs. The oropharyngeal and respiratory muscles are less likely to be affected. There may be retention of urine and feces during a severe attack. Life-threatening cardiac arrhythmias related to hypokalemia may occur during attacks.

1.1.3 Strength may improves if they move around and keep active (“walk it off”). The interval between attacks may be as long as 1 year, or one or more attacks of weakness may occur daily.

1.1.4 The duration of an individual attack varies from a few hours to 24 or 48 hours, muscle weakness is rapidly reversed by correcting the hypokalemia.

1.1.5 In a mild attack, tendon reflexes and electrical reactions of the muscles are diminished in proportion to the degree of weakness. In severe attacks, tendon and cutaneous reflexes are absent and the muscles do not respond to electrical stimulation. Cutaneous sensation is not disturbed.

1.2. Laboratory studies The serum potassium level falls to below 3 mmol/L during an attack. It is essential to test the thyroid function, because hypokalemic periodic paralysis sometimes associated with thyrotoxicosis.

1.3 Electromyography There is a progressive fall in the amplitude of the potential in the long exercise test.

2. Differential Diagnosis

2.1 Acute inflammatory demyelinating polyneuropathy（AIDP） AIDP is an autoimmune process that is characterized by progressive symmetric ascending muscle weakness, hyporeflexia, with or without sensory or autonomic symptoms. Patients may present with facial weakness, dysphagia, dysarthria, ophthalmoplegia, and pupillary disturbances. The CSF often shows a increased protein concentration but a normal cell count. Prolonged distal latencies, conduction velocity slowing, evidence of conduction block, and temporal dispersion of compound action potential are the usual electrodiagnostic features.

2.2 Myasthenia gravis The cardinal features are fluctuating weakness and fatigability of muscles. Patients present with ptosis, diplopia, difficulty in chewing or swallowing, nasal speech, respiratory difficulties. Positive edrophonium test and neostigmine test may be found. Amplitude of the compound muscle action potential deceases following repetitive stimulation.

3 Treatment

3.1 The acute paralysis improves after the administration of potassium. Oral KCl (0.2 to 0.4 mmol/kg) should be given every 30 min. Only rarely is intravenous therapy necessary (e.g., swallowing problems or vomiting present). Administration of potassium in glucose or saline, which may further lower potassium, should be avoided. Mannitol is the preferred vehicle for administration of intravenous potassium.

3.2 A low-carbohydrate, low-sodium diet and avoiding intense exercise may be the way to prevent attacks.

3.3 Acetazolamide may be prescribed to prevent attacks. Potassium should be given as supplements because acetazolamide may cause your body to lose potassium.

reference

Harrison's Principles of Internal Medicine, 18th Edition

Clinical Neurology, 8th Edition

Merritt's Neurology, 10th Edition