Myasthenia gravis (from Greek "muscle",

"weakness", and Latin: gravis "serious";

abbreviated MG) is a neuromuscular disease that
leads to fluctuating muscle weakness and fatigue.

DEFINITION
Myasthenia gravis (MG) is a neuromuscular
disorder characterized by weakness and
fatigability of skeletal muscles. The underlying
defect is a decrease in the number of available
acetylcholine receptors (AChRs) at neuromuscular
junctions due to an antibody-mediated
autoimmune attack.

ETIOPATHOGENESIS
In the most common cases, muscle weakness is
caused by circulating antibodies that block
acetylcholine receptors at the postsynaptic
neuromuscular junction, inhibiting the excitatory
effects of the neurotransmitter acetylcholine on
nicotinic receptors at neuromuscular junctions

ETIOPATHOGENESIS
Alternatively, in a much rarer form, muscle
weakness is caused by a genetic defect in some
portion of the neuromuscular junction that is
inherited at birth as opposed to developing
through passive transmission from the mother's
immune system at birth or through autoimmunity
later in life.[

PRESENTING
COMPLAINTS
Difficulty in;

Breathing
Seeing
Swallowing
Chewing
Walking
Using your arms or hands
Holding up your head

CLINICAL COURSE
The distribution of muscle weakness often has a
characteristic pattern. The cranial muscles,
particularly the lids and extraocular muscles, are
often Involved early in the course of MG, and diplopia
and ptosis are common initial complaints. Facial
weakness produces a snarling expression when the
patient attempts to smile. Weakness in chewing is
most noticeable after prolonged effort, as in chewing
meat. Speech may have a nasal timbre caused by
weakness of the palate or a dysarthric mushy
quality due to tongue weakness. Difficulty in
swallowing may occur as a result of weakness of the
palate, tongue, or pharynx, giving rise to nasal
regurgitation or spiration of liquids or food.

 Bulbar weakness is especially prominent in MuSK

antibodypositive MG. In ~85% of patients, the
weakness becomes generalized, affecting the limb
muscles as well. If weakness remains restricted to
the extraocular muscles for 3 years, it is likely
that it will not become generalized, and these
patients are said to have ocular MG. The limb
weakness in MG is often proximal and may be
asymmetric. Despite the muscle weakness, deep
tendon reflexes are preserved. If weakness of
respiration becomes so severe as to require
respiratory assistance, the patient is said to be in
crisis.

Dx
DIAGNOSIS OF MYASTHENIA GRAVIS (MG)
History

Diplopia, ptosis, weakness

Weakness in characteristic distribution
Fluctuation and fatigue: worse with repeated activity,
improved by rest
Effects of previous treatments

Physical examination

Ptosis, diplopia
Motor power survey: quantitative testing of muscle
strength
Forward arm abduction time (5 min)
Vital capacity

Absence of other neurologic signs

Anticholinesterase test (Edrophonium)
Laboratory testing
Anti-AChR radioimmunoassay: ~85% positive in generalized MG; 50% in
ocular MG; definite diagnosis if positive; negative result does not exclude MG.

DDx
nonautoimmune
CMS discussed above, drug-induced myasthenia,
Lambert Eaton myasthenic syndrome (LEMS),
neurasthenia, hyperthyroidism,
botulism, intracranial mass lesions, and
progressive external ophthalmoplegia.

Tx
ANTICHOLINESTERASE PYRIDOSTIGMINE 3060mg t.d or q.d
THYMECTOMY
IMMUNOSUPPRESSION GLUCOCORTICOIDS
(Prednisolone 15-25mg/d)
MANAGEMENT OF M.G. CRISIS

PARKINSONS DISEASE

PARKINSONS DISEASE
Parkinsons disease (PD) is the most common
form of a group of progressive neurodegenerative
disorders characterized by the clinical features of
parkinsonism, including bradykinesia (a paucity
and slowness of movement), rest tremor,
muscular rigidity, shuffling gait, and flexed
posture.

EPIDEMIOLOGY
PD afflicts ~1 million individuals in the United
States
(~1% of those older than 55 years). Its peak age
of onset is
in the early 60s (range 3585 years), and the
course of the
illness ranges between 10 and 25 years.

ETIOLOGY
GENERALLY UNKNOWN
GENE THEORY
ENVIRONMENTAL TRIGGERS

PATHOGENESIS
(1) genetic vulnerability (e.g., abnormal
processing or folding of -synuclein; Fig. 24-3,
steps i, ii);
(2) oxidative stress (steps iv, v);
(3) proteasomal dysfunction (step iii);
(4) abnormal kinase activity (step vi); and
(5) environmental factors, most of which have yet
to be identified.

THREE (3) CARDINAL

SIGNS
Rest tremor, Rigidity, and Bradykinesia

OTHER SYMPTOMS

MICROGRAPHIA
DYSPHASIA
IMPAIRED POSTURE AND BALANCE
LOSS OF AUTOMATIC MOVEMENT

Dx
PATIENT HISTORY / FAMILY HISTORY- confirm
genetic and environmental influence
NEUROLOGICAL / PHYSICAL EXAM- confirm
symptoms
ULTRASOUND OF BRAIN
MRI OF BRAIN
CT SCAN OF BRAIN
SPECT & PET SCAN

Tx
Carbidopa-levodopa.
Dopamine agonists.- Ropinorole
Pramiprexole
MAO-B inhibitors.- Selegiline
Catechol-O-methyltransferase (COMT)
inhibitors. Entacapone
Anticholinergics Amantadine
Surgery - Deep Brain Stimulation