5.Clinical findings in examination of Parkinson disease

Management of Guillain barre syndrome...
a. Immediate management of patients with AIDP focuses
on close monitoring and supportive care
1) Serial maximal respiratory pressures and forced vital
capacities (FVC)2) Mechanical ventilation and intensive care for precipitous decrease in any measure or low respiratory values
(FVC <20 mL/kg, maximal inspiratory pressure <30
mm Hg, or maximal expiratory pressure <40 mm Hg)
3) Management of autonomic instability: labile blood
pressure, cardiac arrhythmias (cardiac monitoring
required), urine retention, and ileus
4) Management of pain (very common symptom in
acute and plateau phases of care): refractory pain may
be treated with antiepileptic medications; short-term
narcotics may be necessary
b. Management of disease course: immunomodulation
1) Corticosteroids have never been conclusively shown
to help shorten disease course or minimize morbidity
2) Intravenous immunoglobulin and plasmapheresis are
likely equally effective in mitigating disease severity
and should be instituted early
..Both intravenous immunoglobulin (IVIG; 0.4 g/kg/day for
5 days) and plasmapheresis (five to six exchanges over
1–2 weeks) appear equally effective when given within the
first 2 weeks after onset. Combination therapy consisting
of both does not provide additional benefit. Plasmapheresis
may be precluded in hemodynamically unstable patients.
These measures generally increase the pace of recovery,
although their effects on the severity of the disease, the risk of
respiratory and autonomic dysfunction, and ultimate disability are less clear.

إجابات نموذجية
من دافيدسون ،وكرنت وهاريسون وكتاب البورد

محاضرة hyperkinetic movement من كلام الدكتور

Medications used in the treatment of Parkinson disease:


🔳Dopaminergic agents
◾️1-Dopamine precursor:
▪️Levodopa (with carbidopa)
-Itis the most potent agent for the symptomatic treatment of PD.
-MOA: it's converted in the body to dopamine by enzymatic reaction.
-S.E:
1)The most common early side effects are nausea, vomiting, and hypotension, but cardiac arrhythmias may also occur.
2)Dyskinesias, restlessness, confusion, and other behavioral changes tend to occur later.
3)Wearing off effect or on-off phenomenon occurs later.
It isn't used alone due to rapid breakdown in periphery, so we add Carbidopa which inhibits the enzyme responsible for the breakdown of levodopa to dopamine, does not cross the blood-brain barrier. E.g. Sinemet(L-dopa + Carbidopa).
-Contraindications:
1) Patients with psychotic illness.
2)Patients with narrow-angle glaucoma.

◾️2-Dopamine agonists:
▪️E.g.Bromocriptine, pramipexole, ropinirole, amantadine, apomorphine.
-MOC: act directly on dopamine
receptors.
-Their use is associated with a lower incidence of the response fluctuations and dyskinesias that occur with long-term levodopa therapy.
-S.E: fatigue, somnolence, nausea, peripheral edema, dyskinesias, confusion, and postural hypotension.

◼️3-COMT inhibitor:"Catecholamine-O-methyltransferase ":
◾️E.g.Entacapone, tolcapone.
-MOA: reduce the metabolism of levodopa to 3-O-methyldopa and thereby alter the plasma pharmacokinetics of levodopa.
S.E: Diarrhea is serious, fulminant hepatic failure especially with tolcapone.
-It is not effective as a monotherapy,so we use it as a combination: Stalevo (L-dopa+Carbidopa+entacapone)

◼️4-Selective monoamine oxidase inhibitors"MAO-B inhibitor":
◾️E.g.Selegeline, rasagiline.
-MOA: reduces catabolism of dopamine in brain, with decreased demand for L-dopa.
-S.E: headache, dyskinesias, hallucinations.

🔳Nondopaminergic
agen
◼️1-Anticholinergic:
▪️E.g.Trihexyphenidyl, diphenhydramine, amitriptyline.
-MOA: inhibition of excitatory cholinergic neurons leads to decrease concentration of Ach.
-Are more helpful in alleviating tremor and rigidity than bradykinesia in patients <60 years.
-S.E: confusion, forgetfulness, blurred vision, constipation, dry mouth, urinary retention, hallucinations, and psychosis.

◼️2-Antiglutaminergic:
▪️E.g.Amantadin
-Treatment for LD-induced dyskinesias.
-S.E: livedo reticularis, peripheral oedema, delirium and other anticholinergic effects.

◼️3-GABAergic drug:
▪️E.g.Lorazepam or clonazepam
-For Confusion and psychotic symptoms may occur as a side effect of dopaminergic therapy or as a part of the underlying illness.

🔳Atypical neuroleptic
◼️Serotonin and dopamine antagonist:
▪️E.g. Quetiapine
-The most commonly used agent for treatment of mild to moderate hallucinations is quetiapine.
-Also for insomnia.

Diagnosis of Myasthenia Gravis (MG):

History
1-Diplopia, ptosis, dysarthria, dysphagia, dyspnea.
2-Weakness in characteristic distribution: proximal limbs, neck extensors, generalized.
3-Fluctuation and fatigue: worse with repeated activity, improved by rest.
4-Effects of previous treatments.

Physical examination
1-Ptosis, diplopia, objective diplopia.
Expressionless face. Myasthenic sneer.
2-Motor power survey: quantitative testing of muscle strength.
3-Forward arm abduction time (5 min),weakness.
4-Vital capacity measurement.
5-Absence of other neurologic signs.

Laboratory testing
1)Serologic testing :
a.Anti-AChR–binding antibodies :
-Highly sensitive for MG: most specific test, often used for screening .
-85% positive in generalized MG.
-50% positive in ocular MG.
-Definite diagnosis if positive; negative result does not exclude MG.
b.Anti-MuSK antibodies :
-40% of AChR antibody–negative patients with generalized MG have anti-MuSK antibodies.

2) Repetitive nerve stimulation(RNS):
-Decrement of >15% at 3 Hz: highly probable.

3)Single-fiber electromyography(SFEMG):
-Blocking and jitter, with normal fiber density ; confirmatory, but not specific.

4)Edrophonium chloride"Tensilon":
- (2 mg + 8 mg IV) highly probable diagnosis if unequivocally positive.

5)Chest computed tomography (CT):
-Exclude thymoma(all patients) .

6)Ice pack test "Ocular Cooling ".

7)Routine nerve conduction studies (NCSs):
a. Motor: usually normal compound muscle action potential (CMAP), conduction velocity, and distal latency, but low CMAP may be found in severe MG.
b. Sensory: normal .

☝️
🔺 In NEUROMUSCULAR DISEASES
Number 12 (the correct D) .

Immunotherapy in Neurological diseases:

-Immunotherapy is the treatment of disease by activating or suppressing the immune system.
-Two forms:
1)Activation immunotherapies:
Elicit or amplify an immune response.
E.g. chemotherapy in treatment of some brain tumors.
2)Suppression immunotherapies:
Reduce or suppress immune response.
E.g.Immunosuppressive drugs such as Glucocorticoids.

-Immunomodulators: are the active agents of immunotherapy.

Examples of different modalities used in the management of neurological diseases:

1)Glucocorticoid treatment:
E.g.Prednisone, methylprednisolone.
1-In acute attack of Multiple sclerosis.
2-Long treatment in myasthenia gravis.
3-Bell's palsy.
4-Temporal arteritis.
5-Cluster headache.
6-SLE, dermatomyositis,polymyositis.
7-Some epilepsy syndromes,such as West syndrome" ACTH".
8-Becker muscular dystrophy.

2)Pharmacological immunosuppression treatment:
Eg.Azathioprine , mycophenolate mofetil.
Used in:
1-Myasthenia gravis.
2-Neuromyelitis optica (Devic's disease).
3-SLE.
4-Dermatomyositis,polymyositis.
5-Behçet's disease.


3)Intravenous immunoglobulin(IVIG):
-It is the use of a mixture of antibodies (immunoglobulins) to treat a number of health conditions.
Conditions in which used:
1-Guillain-Barré Syndrome.
2-Chronic inflammatory demyelinating polyneuropathy.
3-Multifocal motor neuropathy.
4-Stiff person syndrome,
5-Multiple sclerosis
6-Acute exacerbation of myasthenia gravis"short term".
7-Dermatomyositis and polymyositis.

4)Plasmapheresis:
-It's a broad range of procedures in which extracorporeal separation of blood components results in infiltrated plasma product.
Indications:
1-GBS.
2-Myasthenia gravis.
3-Chronic inflammatory demyelinating polyneuropathy.
4-Wilson's disease.
5-Lambert–Eaton myasthenic syndrome .
6-Multiple sclerosis.
7-Neuromyelitis optica.
8-Transverse myelitis.
9-HIV-related neuropathy.
10-Acute disseminated encephalomyelitis (ADEM).
11-Antiphospholipid antibody syndrome (APS or APLS).


5)Cytokine "interferon-beta-1":
-In treatment of Multiple sclerosis.

6)Monoclonal antibodies:
E.g Ocrelizumab, Alemtuzumab,etc
-In Treatment of Multiple sclerosis.

🔳=Class
◼️=Group
▪️=Drug

Management Strategies of Guillain-Barré Syndrome:


a.Immediate management of patients with AIDP"Acute inflammatory demyelinating polyneuropathy" focuses on close monitoring and supportive care:
1) Serial maximal respiratory pressures and forced vital capacities (FVC)
2) Mechanical ventilation and intensive care for precipitous decrease in any measure or low respiratory values: (FVC <20 mL/kg, maximal inspiratory pressure <30 mm Hg, or maximal expiratory pressure <40 mmHg).
3) Management of autonomic instability:
-Labile blood pressure, cardiac arrhythmias (cardiac monitoring required), urine retention, and ileus.
4) Management of pain:
-Very common symptom in acute and plateau phases of care.
-Refractory pain may be treated with antiepileptic medications; short-term narcotics may be necessary.

b. Management of disease course: Immunomodulation
1-Intravenous immunoglobulin:
-(IVIG; 0.4 g/kg/day for 5 days)
-IVIG is often the initial therapy chosen because of its ease of administration and good safety record.
-IVIG may be preferable to plasma exchange (PE).

2-Plasmapheresis:
-(Five to six exchanges over1–2 weeks)
-Intravenous immunoglobulin and plasmapheresis are likely equally effective in mitigating disease severity and should be instituted early and appear equally effective when given within the first 2 weeks after onset.
-Combination therapy consisting of both does not provide additional benefit.
-Plasmapheresis may be precluded in hemodynamically unstable patients.
-These measures generally increase the pace of recovery, although their effects on the severity of the disease, the risk of respiratory and autonomic dysfunction, and ultimate disability are less clear.
-Do not give IVIG then PE,because PE will wash IG.

3-Corticosteroids:
-Have not been found to be effective in GBS.

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