1. CSF is formed by active secretion by choroids plexus in the lateral ventricles then → pass via foramen of Monro to the 3rd ventricle → then via aqueduct of Sylvius to the 4th ventricle → then via foramena of Inuscka & Magendi to the subarachnoid space.

1. Muscle diseases
Proff. Of neurologist
Aied mottib al-oboidy

2. objectives
•
1.define approach to myopathy
•
2.recognize the inflammatory myopathy.
•
3-mention clinical manifestations of myopathy.
•
4-recognize investigations and treatment.

4. •
Negative
–
Weakness
–
Fatigue
–
Exercise intolerance
–
Muscle atrophy
•
Positive
–
Myalgia
–
Cramps
–
Contractures
–
myotonia
–
myoglobinuria

5. .1
Weakness:
(a
Proximal lower extremities:

difficulty climbing stairs, arising from a low chair or
toilet, or getting up from a squatted position.
(b
Proximal upper extremities:

trouble lifting objects over their head and brushing
their hair.
(c
Distal upper extremities:

difficulty opening jars, inability to turn a key in the
ignition.
(d
Distal lower extremities:

tripping due to footdrop.
(e
Cranial muscle weakness,
(f
ysarthria, dysphagia, or ptosis.

6. DEFINITION
Polymyositis (PM) is a chronic idiopathic form of
inflammatory myopathy, leading to progressive
muscle weakness. Dermatomyositis (DM) is a
closely related disorder characterized by
inflammatory changes in both the muscle and skin.

7. EPIDEMIOLOGY
-- Incidence :
0.5–1.0 cases per 100 000 patient-yrs.
-- PM/DM affects all age groups, including children
-- In adults, disease incidence increases with age
-- slight female to male predominance (∼2:1).
-- Both PM and DM have been reported to co-
occur with malignancy, most commonly
adenocarcinomas .

8. ETIOLOGY
-- The etiology of PM/DM is not well understood.
-- Environmental factors speculated to play a
role in PM/DM include select infections
(toxoplasmosis, Epstein–Barr virus) .
-- in addition to exposure to other exogenous
toxins/chemicals.
-- PM/DM does not display significant familial
clustering.

9. PATHOGENESIS
-- an initial muscle injury leads to
the presentation of an ‘auto antigen’.
-- This antigen is thought to be processed and
presented to T cells in the context of MHC class
I.
-- Once activated, T cells in PM/DM synthesize
interferon-γ, which in turn leads to increased
expression of proinflammatory cytokines
including IL-1 and TNF.

10. CLINICAL PICTURE
-- Insidious onset , and progressive muscle
weakness, often in the absence of pain.
-- Muscle weakness : is most prominent in proximal
muscle groups, leading to problems with climbing
/descending stairs or rising from a seated position.
- Although distal muscle weakness can occur with
disease progression, a suggestive
history (e.g. weakness in grip, dropping things)
should prompt an assessment of alternative
etiologies

11. -- Skin involvement or rash in DM can occur at any
time point relative to the onset of weakness.
-- Generalized symptoms may include progressive
fatigue, fevers, RP, and weight loss.
-- ‘DM sine myositis’ :is typical DM skin
involvement ,occur in the absence of apparent
Myopathy (a myopathic DM).

12. Other extra skeletal muscle involvement:
- Arthralgias: related to an inflammatory arthritis;
- Dysphagia: due to esophageal involvement; -
Dyspnea: and/or dry cough related to either
pulmonary (e.g. interstitial lung disease [ILD]) or
cardiac involvement (pericarditis or
myocarditis).

13. Examination
• Symmetric weakness in proximal muscle
groups.
• Skin involvement :
• Gottron’s papules (pathognomonic of DM);
palpable erythematous lesions over the extensor
surfaces of [MCP] and [PIP] joints,
elbows, or knees.
• Gottron’s sign: non palpable rash, similar
distribution to Gottron’s papules.

14. Grotton’s Sign
Nail Changes (Capillary
(
Loop Dilatation

15. Examination
• Heliotrope rash :occurs around the eyes.
• Erythroderma.
• V-sign , shawl sign, and ‘mechanics hands’
• Calcinosis (more common in juvenile DM).
• Extra muscular or end-organ involvement:
arrhythmia or gallop suggestive of cardiac
involvement; lung crackles suggestive of
pulmonary disease.

16. Heliotrope rash
-- A reddish-purple
eruption on the
upper eyelid
-- accompanied by
swelling of the
eyelid
-- Most specific
rash in DM
•
Heliotrope rash

17. Generalized Erythroderma
Facial erythema

18. V sign: Erythematous rash around
face, neck and anterior chest
Shawl sign: erythematous rash
affecting upper back

19. Mechanic’s hands: Cracking of the finger pad skin,
commonly involving the first, second, and third fingers
roughened, cracked skin at tips and lateral aspects of the
fingers resulting in irregular, dirty-appearing lines

21. Inclusion body myositis
- Is a rare form of inflammatory myopathy
that shares many clinical similarities with PM
(progressive weakness, increased incidence with
age).
- IBM typically results in ‘lower grade’ elevations in
muscle enzymes, can be less symmetric, and
involves distal muscle groups. It is far more
refractory to treatment (with a resulting poor
prognosis) compared with PM/DM.

22. Criteria for the diagnosis
1- Symmetric weakness,
progressive, Involving the
proximal muscles
2 -Muscle biopsy indicative of
inflammatory myopathy
3- Elevation of muscle enzymes on
laboratory examination
4- EMG : findings suggestive of
inflammatory myopathy.
5- Characteristic skin findings of DM (e.g.
heliotrope rash, Gottron’s papules, or
Gottron’s sign).

23. Patients are said to have :
--‘definite’ inflammatory myopathy
if criteria 1–4 are present (1–5 for DM);
--‘probable’
if three of the first four criteria are met
(plus 5 for DM);
-- or ‘possible’
if two of the first four criteria are met
(plus 5 for DM).

24. INVESTIGATIONS
Laboratory
• Although not disease specific, serum
muscle enzymes elevated in the context of
PM/DM include:
• Creatine kinase: often >2-times upper
normal.
• Lactate dehydrogenase.
• Aldolase.
• Aspartate aminotransferase.

25. -- Marked muscle breakdown
due to inflammation may result in increased
myoglobin in serum and urine .
• Acute phase reactants:
ESR and (CRP) are often normal; marked
elevations should raise suspicion for other
causes of inflammation (infection).
• Auto antibodies:
• ANAs: suggestive but not diagnostic of an
underlying CTD (i.e. PM/DM).

26. Myositis specific antibodies
• Anti-t RNA synthetases: in (∼25% of DM);
disproportionate occurrence of ILD, mechanic’s
hands, and RP, (anti-Jo-1) antibody is the most
commonly measured antisynthetase antibody).
• Antisignal recognition protein antibody:
With necrotizing acute-onset polymyositis, cardiac
involvement, and poor ttt response.
• Anti-Mi-2: classic DM; excellent ttt response.

27. EMG and MRI
• The characteristic ‘triad’ of EMG
include the presence of
1) short, small, low-amplitude polyphasic
motor units;
2) fibrillation potentials; and
3) atypical high-frequency repetitive discharges.
-Tests of nerve conduction velocity (NCVs)
performed in conjunction with EMG are helpful in
ruling out a neuropathic etiology.

28. -MRI
- MRI short T1 inversion recovery (STIR) may
be an alternative means for detecting inflammatory
muscle changes.
- Neither EMG nor MRI are diagnostic, but are most
helpful in identifying sites for biopsy.
• Muscle biopsy: Most often done in the
quadriceps or deltoid muscles.
• Skin biopsy: Skin biopsy may be useful
with atypical presentations (e.g. DM sine
myositis)

29. Other laboratory or imaging tests
--Age appropriate cancer screening should be
performed.
-- imaging of the chest, abdomen, and pelvis in
evaluating for occult malignancy.
-- Patients presenting with dyspnea or chronic cough
may need (chest radiograph, pulmonary function
tests, electrocardiogram [ECG],
echocardiogram).
--Patients with marked dysphagia may require further
endoscopic examination.

30. PROGNOSIS
Overall survival has improved, now exceeding
80–90%.
Poor prognostic factors include:
- co-occurrence of malignancy
- older age at onset
- female gender,
-severe end organ involvement (dysphagia,ILD).
- the presence of antisynthetase or(anti-SRP) AB. -
IBM has a particularly poor prognosis.

31. MANAGEMENT
Primary therapy includes
• Systemic GCs (e.g. prednisone, 1–2 mg/
kg/day); maintained, until normalization of muscle
enzyme; gradually tapered over the
course of several months to years.
• Methotrexate (MTX) or AZA; used concomitantly with
GCs; may allow for more rapid GC tapering.
• HCQ: possible utility in skin disease
• IVIG (0.5–1.0 g/kg/day): sometimes
used as induction therapy in severe or
refractory disease; possible role in IBM.

32. -- Physical therapy and sun avoidance
for those with photosensitivity.
• Second-line treatments used with limited
data include cyclosporine, tacrolimus,
MMF, anti-TNF agents, and B cell depletion
(rituximab).
-Disease flares or recurrence can occur during
GC tapering and/or withdrawal. Disease flare
can be confused with steroid-induced myopathy.