Translate

Saturday, 15 December 2012

HACEK GROUP


·         Gram –ve + Capnophilic
·         Normal flora of oral cavity therefore, can cause local infections.
·         Most common severe systemic infection is Subacute Infective Endocarditis of both native and prosthetic valves.
·         Most common valves – Aortic and Mitral valves
·         Embolization is common
·         Diagnosis-
§  Culture
§  PCR (e.g. heart valves)
·         Antibiotic susceptibility should always be done. (E-test methodology used)
·         Treatment should be for
§  Native Valves endocarditis - 4 weeks
§  Prosthetic Valve endocarditis - 6 weeks


HACEK GROUP
CHARACTERISTICS
TREATMENT
INITIAL
ALTERTNATIVE
Haemophilus spp.
·         H. aphrophilus (requires factor X) and H. parainfluenzae (requires factor V) are the most common isolated.
Ceftriaxone (2g/day)
Ampicillin + Sulbactam/ Fluoroquinolones
Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans
·         Associated with periodontal abscess and dental procedures
Ceftriaxone
Ampicillin + sulbactam/ Fluoroquinolones
Cardiobacterium hominis
·         Valvular heart disease + Prosthetic valves
·         Aortic valve (M.C.)
Ceftriaxone
Ampicillin + Sulbactam
Eikenella corrodens

Ampicillin
Ceftriaxone/ Fluoroquinolones
Kingella kingae


Fluoroquinolones


Monday, 22 October 2012

KAWASAKI DISEASE



·         Medium-vessel vasculitis (predilection for coronary arteries)
·         a.k.a. Mucocutaneous Lymph node Syndrome or Infantile Polyarteritis Nodosa.
·         Most common cause of acquired heart disease in children in US & Japan (Kawasaki > Acute Rheumatic Fever)
·         Most common age of presentation - ≤ 2 yrs (80% cases < 5yrs)
·         Pathogenesis and Pathology-
§  Transmural inflammation with destruction of the internal elastic lamina.
§  Predominance of macrophages and lymphocytes (CD8 T cells + IgA plasma cells)
·         Clinical Features


PHASES OF KAWASAKI DISEASE
Acute phase
·         Febrile phase
·         Lasts for 1-2 wk
·         Edema + erythema + lymphadenopathy + rash
Subacute phase
·         Starts once acute phase is over.
·         Lasts till 4th wk. (after disease onset)
·         Phase with the highest risk of sudden death
·         Desquamation + Thrombocytosis + Coronary artery aneurysm development
Convalescent phase
·         From end of all clinical signs of illness to returning of ESR back to normal.
·         Lasts till 6-8 wks (after disease onset)

  
DIAGNOSTIC CRITERIA
FEATURES
Fever lasting for at least 5 days
High grade
Lasts for 1-2 wk (maybe up to 3-4 wk)
Prolonged fever - ↑ risk of Coronary Artery Disease (CAD)
PLUS

Presence of at least 4 out of 5 clinical features given below :-

1.       Bilateral nonpurulent bulbar conjunctival congestion

2.       Involvement of oropharyngeal mucosa – congestion of pharynx, erythema and/or dry fissured lips, strawberry tongue
Perineal desquamation (acute phase)

3.       Involvement of the peripheral extremities - edema and/or erythema of the hands or feet in the acute phase; or periungual desquamation in the subacute phase


4.       Polymorphous, nonvesicular rash/exanthema (primarily truncal)
Accentuated in groin
5.       Acute non-purulent cervical lymphadenopathy - ≥1.5 cm (usually unilateral)




OTHER CLINICAL FEATURES
·         Most important manifestation
·         Myocarditis (50%) – Ventricular dysfunction and tachycardia
·         Coronary artery aneurysm (25%) and thrombosis (greatest risk of complications with aneurysm ≥ 8mm internal diameter)
·         Pericarditis
·         Myocardial ischemia and infarction
Arthritis
·         Female > Male
Aseptic meningitis
·         More common in Infants
Urethritis + meatitis + sterile pyuria
·         Infants


·         Cause of death – (2.8%)
§  Myocardial infarction
§  Coronary aneurysm rupture
·         Poor prognostic factors
§  Male
§  Age < 1 yr
§  Prolonged fever
§  Recurrent fever (after an afebrile period)
§  Laboratory values at presentation:
§  ↓ Hb
§  ↓ Platelets
§  ↑ Neutrophil and band counts
§  ↓ Albumin and age-adjusted serum IgG levels.
·         Diagnosis
§  Clinical - based on diagnostic criteria mentioned above.
§  Lab Findings –  (characteristic features)
§  Acute phase- (may persist for 4-6 wk i.e. during subacute & convalescent phase)
·         ↑ ESR
·         ↑ C-reactive protein
·         Anemia (normocytic)
§  Subacute phase-
·         Thrombocytosis (may exceed 1,000,000/mm3)
§  Radiological
§  Two-dimensional echocardiography
·         Most important test to monitor the potential development of coronary artery lesions.
·         Performed at time of presentation with follow-ups at end of each clinical phase.
·         Treatment


PHASE
TREATMENT
Acute phase
Intravenous Immunoglobulin (2 g/kg single infusion over 10-12 hr)
+
Aspirin (100 mg/kg per day for 14 days)
Convalescent Phase
Aspirin (3-5 mg/kg once daily orally until 6-8 wk after illness onset)
Acute Coronary Thrombosis
Prompt Fibrinolytic Therapy with tissue plasminogen activator, streptokinase, or urokinase
Long-term therapy in coronary abnormalities
Aspirin (3-5 mg/kg once daily orally)
±
Dipyridamole (4-6 mg/kg/24 hr divided in two or three doses orally)
±
Warfarin (high risk of thrombosis)
Coronary Artery Aneurysms
Surgery
Coronary Artery Stenosis
Surgery
·         Catheter intervention with percutaneous transluminal coronary rotational ablation.
·         Directional coronary atherectomy + stent implantation.

Thursday, 11 October 2012

MULTIPLE SCLEROSIS


·         Demyelinating disorder of CNS
·         M:F = 1:3
·         Age of onset- 20-40 yrs
·         Pathogenesis
§  Δiad-
1.       Inflammation
2.       Demyelination
3.       Gliosis
§  Stage of inflammation-
§  Perivenular cuffing with inflammatory mononuclear cells (T cells & macrophages) + infiltration of surrounding white matter
§  Disruption of blood brain barrier (but vessel wall is preserved, a contrast to vasculitis syndromes where vessel wall is damaged)
§  Stage of demyelination
§  Cell-mediated immunity- T-lymphocytes against Myelin Basic Protein (MBP)
§  Humoral immunity- Myelin specific antibodies
§  Stage of Gliosis/Scarring
§  Astrocytes proliferation + Partial remyelination of surviving naked axons by surviving oligodendrocytes appearing as ‘shadow plaques’
·         Histology
·         Risk factors-
§  Vit D deficiency
§  Genetic susceptibility
§  HLA DR2
§  IL2RA (Interleukin-2 receptor α gene)
§  IL7RA (Interleukin-7 receptor α gene)
§  High socioeconomic status
·         Clinical Manifestations
§  Weakness of the limbs
§  UMN type
§  Exercise induced weakness- characteristic
§  Spasticity (associated with)
§  Painful spasms
§  Spontaneous/Movement induced muscle spasms
§  Facial weakness
§  Due to lesion in pons.
§  Not associated with ipsilateral loss of taste sensation/retroauricular pain (a contrast to Bell’s palsy)
§  Cerebellar features
§  Ataxia
§  Dysarthria / Scanning speech
§  Vertigo
§  Sensory symptoms
§  Paresthesias (pins-needles, formications, burning pain)
§  Hypoesthesia (numbness)
§  Pain (50%)
§  Bladder dysfunction (>90%)
§  Detrusor hyperreflexia - impairment of suprasegmental inhibition. (urgency, nocturia, frequency)
§  Detrusor sphincter dyssynergia - loss of synchronization between detrusor and sphincter muscles. (hesitancy, urinary retention, overflow incontinence)
§  Constipation (30%)
§  Sexual Dysfunction
§  Cognitive Dysfunction and Depression
§  Optic neuritis
§  Diminished visual acuity
§  Desaturation/↓color vision in central field of vision.
§  Unilateral > Bilateral
§   Visual loss is usually preceded by periorbital pain (aggravated by eye movements)
§  Pallor of optic disk/optic atrophy
§  Visual blurring


§  Ancillary Symptoms
§  Heat Sensitivity-
·         Neurologic symptoms are produced when core body temperature rises.
·         Uhthoff’s symptom- Unilateral visual blurring during exercise or hot shower.
§  Lhermitte’s Symptoms- electric shock–like sensation (specially induced by flexion or other movements of the neck) radiating down the back into the legs
§  Trigeminal Neuralgia and Glossopharyngeal Neuralgia (demyelination of CN 5th and 9th)
§  Hemifacial Spasm (Demyelination of CN 7th)
§  Facial Myokymia – persistent rapid flickering contractions of facial muscles (due to lesions of brainstem or corticobulbar tracts)
·         Disease Patterns
1.       Relapsing/Remitting MS (85%)
§  Discrete attacks separated by intervals of near complete recovery
§  Risk of evolving to SPMS is ≈ 2% every year
§  Majority of RRMS progress to SPMS.

  
2.       Secondary Progressive MS
§  Always starts as RRMS, but with time there is gradual progression of baseline disability with time which is unassociated with acute attacks of MS
§  Thus, SPMS represents late stage of RRMS.



3.       Primary Progressive MS (15%)
§  There are no acute exacerbations/attacks of MS. Instead, from the onset there is a gradual progression of disability with time, which is usually rapid than SPMS.
  
4.       Progressive/Relapsing MS (5%)
§  Overlapping between PPMS and SPMS disease patterns.
  
·         Diagnosis
§  MRI with/without Gadolinium contrast
§  In Active lesions – BBB disrupted → Gd contrast leakage into surrounding brain parenchyma → enhancement on T1-weighted MRI
§  Residual MS plaquehyperintense focal area on T2-weighted MRI (but only 1/3rd appear as hypointense lesions on T1-weighted MRI → ‘Black Holes’)
§  Burden of Disease a.k.a. degree of Clinical Disability – correlates weakly with the total volume of T2 hyperintense lesions.
§  Evoked Potential testing
§  To assess function of afferent pathways (visual, auditory or somatosensory) and efferent pathways(motor)
§  CSF examination
§  ↑ mononuclear cells (mononuclear pleocytosis)
§  CSF total proteins normal/mildly ↑
§  ↑ level of intrathecally synthesized IgG (to distinguish between intrathecally derived IgG and Serum IgG which may have leaked into CSF due to disruption of BBB)
·         CSF IgG index = [IgG : Albumin]CSF ÷ [IgG : Albumin]Serum
·         CSF IgG synthesis rate
·         OligoclonalBanding (OCB) – detected by Agarose gel electrophoresis - ≥2 OCBs – seen in 75-90 % of MS patients.
·         Treatment
§  Degree of neurological impairment - Kurtzke Expanded Disability Status Score (EDSS)
§  Score < 3.5 – mostly seen in RRMS
§  Score > 5.5 – mostly seen in PPMS or SPMS
§  Treatment of Acute Attacks
§  Differentiate between ‘True-exacerbation’ and ‘Pseudo-exacerbation’
§  True-exacerbation or acute active disease – Glucocorticoids (mainstay)
§  Glucocorticoids avoided in ‘Pseudo-exacerbation’ [which may be due to temperature changes/fever/infection]
§  Reducing Biological Disease Activity via Disease Modifying Agents (FDA approved)
§  IFN-β (flu-like symptoms, hepatotoxicity) (not effective in SPMS without acute attacks)
·         IFN-β-1a (RRMS/SPMS with acute attacks)
·         IFN-β-1b (RRMS/SPMS with acute attacks)
§  Glatiramer acetate (RRMS)
§  Natalizumab (very effective in all forms, but ↑ risk of progressive multifocal leukoencephalopathy on long term therapy)
§  Fingolimod
§  Mitoxantrone (Cardiotoxicity, permanent amenorrhoea, acute leukemia)
§  Cladribine (to be approved by FDA)
§  Symptomatic Therapy