ALL neuro Flashcards
(122 cards)
1
Q
peripheral vs central vertigo
A
- peripheral: position related (stereotypic), +/- hearing abnormal, absence of CNS manifest, severe vertigo, intense n/v
- central: no related to head position change, no hearing abnormal, presence of CNS manifest, less severe vertigo, little or no n/v, presence of cerebellar ataxia
2
Q
ataxia
A
- cerebellar ataxia: wide-based gait, dysmetria, poor motor coordinate, scanning speech, truncal ataxia
- sensory ataxia: ataxia worsen while cutting off visual input (หลับตา)
- vestibular ataxia: accompany w vertiginous symptom (vertigo, n/v, oscillopsia ภาพสั่น)
3
Q
clinical course
A
- sudden, acute: vascular, traumatic
- acute progressive: inflam (infect or non-infect)
- chronic progressive: neoplastic, degenerative
4
Q
cause of ischemia - global
A
cause: hypotension, shock, cardiac arrest → inadequate cerebral perfusion
-
selective vulnerable of neuron กาก บอบบาง
- hippocampus neuron (CA1 region) เกี่ยวกับ memory impairment
- purkinje cells in cerebellar
- medium-sized striatal neurons
- pyramidal neurons in the cortical layers 3,5,6
-
watershed area
- between MCA and ACA, MCA and PCA
- can causing bilateral arm weakness (man-in-barrel syndrome), aphasia
5
Q
cause of ischemia - focal
A
-
disease of the blood vessels
atherosclerosis, carotid dissection, MCA stenosis, reversible cerebral vasocon syndrome, lacunar stroke, perforators -
cardiac embolism
valve disease, myocarditis, Rt to Lt shunt, AF -
disease of the blood components (clot ง่ายไรงี้)
hypercoag, high hct wbc plt
6
Q
adaptation in brain ischemia
A
ไม่แน่ใจว่ามีดีเทลไรกว่านี้มั้ย ;-;
- autoregulation
- increased cerebral blood volume
- normal cerebral blood flow
7
Q
tx in brain ischemia
A
reperfusion
- within 4.5hrs: ยา thrombolysis
- within 6 hrs: mechanical thrombectomy
tissue protection
- stroke unit (for BP management, hydration, etc)
promote plasticity
- rehab
- brain stimulation
- medication
8
Q
สาระน่ารู้ brain ischemia
A
- Afib cause stasis of blood in atria → thrombus formation → embolize to brain
- penumbra zone เซลล์สลบแต่ยังไม่ตาย ยังมีเส้นเลือดบางส่วนมาช่วยเลี้ยง / ischemic core ตายสนิท
- transient ischemic attack (TIA): มีแค่ penumbra zone & no ischemic core → สักพักหายเอง :]
- neuroplasticity: neuron ที่เหลือก้สู้กันต่อไป ~ adjust their activities in response to new situations
9
Q
CN — physical exam
A
- CN I (Olfactory Nerve): Rarely tested; if tested, use aromatic substances like coffee.
-
CN II (Optic Nerve):
- Visual Acuity ชัดชัดช้าดีดีดา: Use Snellen’s chart.
-
Fundoscopy: Assess with an ophthalmoscope for signs of increased intracranial pressure (ICP), such as:
- Papilledema
- Absence of retinal venous pulsation (early sign of ↑ICP).
- Visual Field: Use confrontation testing or perimetry.
-
Light Reflex: Afferent (CN II) → Efferent (CN III).
- Marcus Gunn Pupil: Relative afferent pupillary defect.
3,4,6. CN III, IV, VI (Oculomotor, Trochlear, Abducens):
- Assess extraocular movements (EOM).
-
CN VII (Facial Nerve):
- Lower Motor Neuron (LMN) Lesion: Weakness of both upper and lower face on the same side.
- Upper Motor Neuron (UMN) Lesion: Weakness limited to the lower face.
-
CN VIII (Vestibulocochlear Nerve):
- Hearing: Tuning fork tests (Weber and Rinne) or audiometry.
-
Vestibular Function:
- Vestibulo-ocular reflex tests: caloric test, doll’s eye maneuver.
- Observe for nystagmus.
9-10. CN IX, X (Glossopharyngeal, Vagus Nerve):
- Gag Reflex: Presence indicates an intact reflex.
- Palatal Elevation: Uvula deviates away from the affected side.
-
CN XI (Accessory Nerve):
- Assess the strength of sternocleidomastoid (SCM) and trapezius muscles.
-
CN XII (Hypoglossal Nerve):
- Tongue deviation is toward the affected side in lesions.
10
Q
motor system & Deep Tendon Reflexes (DTR) — physical exam
A
-
Cortex/Corticospinal Tract Lesions:
- pyramidal weakness: upper limb → extensor weaker than flexor / lower limb → flexors weaker than extensors แขนงอขาเหยียด
- Tests for subtle weakness: พวก weak น้อย ๆ
- Pronator drift: pronator ชนะ supinator เลยคว่ำ (normal ppl จะหงายปกติ)
- Forearm rolling test: ข้างปกติจะหมุนแรงกว่า
-
UMN Syndrome (ทั้งหมดเป็น motor long tract sign)
- hyperreflexia (for DTR) แต่ๆๆ อาจไม่ขึ้นใน acute severe lesion or pre-existing peripheral neuropathy
- Babinski sign นิ้วโป้ง uppppp
- Sustained ankle clonus ข้อเท้ากระตุก ๆๆ
- LMN Syndrome: Flaccid weakness with hyporeflexia or areflexia, can be found fasciculation
11
Q
sensory system — physical exam
A
- Joint Proprioception: Small joint testing or Romberg test หลับตาแล้วล้ม
- Vibration: Use a tuning fork.
- Pinprick Sensation: Assess sharp/dull differentiation.
- Trigeminal Nerve (CN V): Sensory testing over facial dermatomes.
12
Q
speech — physical exam
A
- dysarthria: motor speech disorder characterized byslurred or unclear speechdue to muscle weakness พูดไม่ชัดเพราะกล้ามเนื้อแย่
- dysphasia/aphasia: language disorder affecting ability tounderstand or produce language despite intact speech mechanics — wernicke ไม่ก้ broca พัง
13
Q
cerebellar function — physical exam
A
-
vermis lesion: truncal ataxia แกนกลาง
- difficulty sitting upright without support โอนไปเอนมา
-
hemisphere lesion: Ipsilateral limb ataxia รยางค์
- tests: finger-to-nose, heel-to-shin, rapid alternating movements คว่ำหงายมือ (dysdiadochokinesia), overshooting
-
both vermis & hemisphere
- cerebellar gait ataxia: wide-based appearance, tandem gait test เดินเท้าต่อเท้าบนเส้นเดียว 🩰
14
Q
gait analysis — physical exam
A
- cerebellar ataxic gait: wide-based, unsteady
- parkinsonian gait: shuffling, reduced arm swing, stooped posture
- gait apraxia: magnetic, frontal gait, difficulty initiating step ที่อจให้ดูคลิป เหมือนแม่เหล็กจริง //pivot
15
Q
cortical sign — physical exam
A
-
Frontal Release Signs: prefrontal cortex dysfunction
- grasp reflex เอานิ้ววางบนฝ่ามือแล้วคนไข้จะกำ
- palmomental reflex: ขูด thenar m. แล้ว mentalis m. แถวปากกระตุก
- glabellar tapping sign กระพริบตา
- sucking and snouting reflex อะไรเข้าปากก้ดูดเลย
- อื่น ๆ เช่น aphasia, apraxia, agnosia, neglect, etc.
16
Q
sign of meningeal irritation
A
- neck stiffness: nuchal rigidity คอแข็ง
- kernig’s sign: pain/resistance when extending knee from a flexed hip position ยกขาแล้วตึง
- brudzinski’s sign: hip and knee flexion upon neck flexion งอคอแล้วเข่างอตาม
17
Q
extra-axial sign อจให้ช้อยมาตรง ๆ เลย ห้ามผิดจ้า
A
- cerebrospinal fluid cleft
- displace and expand subarchnoid space
- displace subarachnoid vss
- cortical gray btw mass and white matter
- broad dural base (dural tail sign)
- bony reaction
18
Q
indication for CT head injury or trauma
A
- pt w GCS 13-15 and have at least one of the following: loss of conscious, amnesia to head injury event, witnessed disorientation
- consider CT when: GCS<15 for 2hrs after injury / suspect open or depress skull fracture / any sign of basilar skull fracture (e.g. hemotympanum, raccoon eye, CSF oto-rhinorrhea) / ≥2 episode of vomit / ≥65yo
19
Q
epidural (🍋) vs subdural (🍌) radio
A
- epidural: biconvex (lens) shape, not cross suture unless venous or sutural diastasis/fracture present
- subdural - SDH: crescentic shape, may cross suture, not dural attachment
20
Q
infarc radio
A
acute
- เหมาะสมสุด CT ไว / MRI ช้าแต่ดี เริ่ด พวก infarc เร้ก ๆ เก็บได้หมด / DWI MRI เห็นตั้งแต่ 30mins after onset
- finding: can be normal, hyperdense artery, obscuration of lentiform nuclei, loss of grey-white different (also loss insular ribbon sign) w sulcus effacement, frank hypodense w mass effect
subacute
- wedge shape low density w mass effect, +/- hemorrhagic transformation (BG and cortex), gyral enhancement on postcontrast image
old infarc
- marked low density, volume loss เหี่ยว ๆ
21
Q
meningitis radio
A
- may be normal
- smooth, thickened, intense leptomeninges enhancement, enhancing exudate in sulci and cistern, sulci and basal cistern effacement, mild ventricular enlargement
22
Q
รวมแฟค radio มั้ง
A
- smooth ring enhancing → abscess / necrotic ring enhancing → high grade neoplasm
- sturge-weber’s syndrome: calcification in cortex (tram tract) เด่กปานแดงที่หน้า
- MR spectroscopy (MRS): demon biochem and metabolic change in tissue
- normal pressure hydrocephalus: triad → dementia, ataxia, urinary incontinent
23
Q
position and anatomy for LP
A
- position: pt lies in lateral decubitus position or sits upright with back flexed to expose interspinous space
- anatomy: needle insertion at L3-L4 or L4-L5 interspace / landmarked by line btw iliac crest
24
Q
CSF analysis: normal, indication, abnormal finding
A
-
normal CSF finding
- opening pressure 8-18 cmH₂O
- no RBC, WBC<5 cells/µL (all are lymphocytes)
- protein: 15-45 mg/dL.
- glucose: 45-70 mg/dL (or 40-60% of blood glucose)
-
indications for LP
- diagnostic: suspect of disease in CSF space → meningitis, SAH / for evidence of some CNS disease → neurodegen (e.g. AD)
- therapeutic: CSF release for hydrocephalus or high ICP เจาะเพื่อเทน้ำทิ้ง / lower body anesthesia (spinal block) / เพื่อให้ยา e.g. chemo ABX antifungal
-
CSF Profiles in infectious meningitis
ไปหาอ่านเองจ้า ((จำได้อยุ่ละ))
25
subarachnoid hemorrhage (SAH) vs traumatic tap
**SAH** แดงเถือกทุกอัน
- uniform blood in all vials
- xanthochromia (**yellow discoloration** from hemoglobin breakdown after 6-8hrs)
**traumatic tap** แดงแล้วค่อย ๆ จาง
- blood clears in successive vials.
- no xanthochromia unless delayed processing
26
contraindication, imaging before LP, complication
**contraindication:** risk of brain herniation / skin infection ทำให้คนไข้ meningitis ได้ด้วยตัวเรา / coagulopathy / cardiorespiratory compromise — bc it may affect hemodynamic เพราะทำท่ากุ้ง
**imaging before LP:** focal neurological deficit / increased ICP ดูว่ามี obstruct จุดไหนมั้ย / AoC/ immunocompromise
**complication:** CSF leakage and headache (most common) / brain herniation (most serious) / local or referred pain / cardiorespiratory compromise / bleed / infection / subarachnoid epidermal cyst
27
benefit of electroencephalogram (EEG)
- dx seizure disorder (if not sure)
- classification of seizure disorder
- localization of epileptogenic focus หาจุดกำเนิดการชัก จะได้ผ่าสมองส่วนนั้นออก
- evaluation of prognosis in comatose pt
- (just) alternative brain death confirmation
28
nerve conduction study (NCS) บทเสกนา
- concept: measures speed and strength of nerve signal transmission
- formula
- sensory velocity = distance / latency1
- muscle velocity = distance from 1 to 2 / latency2-latency1
- basic interpretation
- decreased velocity: suggest demyelination (e.g. GBS, chronic inflammatory demyelinating polyneuropathy)
- decreased amplitude: suggest axonal loss (e.g. peripheral neuropathy)
29
repetitive nerve stimulation (RNS)
- decremental response**:** progressive decrease CMAP amplitude w repeat stimuli / เจอใน **MG**
- incremental response: progressive increase CMAP amplitude w repeat stimuli due to improve neurotransmission release / เจอใน **LEMS**
30
electromyogram (EMG)
for measure electrical activity in muscle to differentiate btw
- neuropathic disorder: reduced recruitment, large motor units (e.g. ALS, radiculopathy)
- myopathic disorder: early recruitment, small motor unit (e.g. muscular dystrophy, myositis)
31
compensatory mechanism เมื่อมี intracranial space occupying lesion
- hyperventilation → PCO2↓ → cerebral vasocon → Intravascular blood volume ↓
- vein collapse หรือตีบเล็กลง
- increasing rate absorption of CSF & CSF บางส่วนถูกไล่ไปอยู่ใน spinal subarachnoid space → ปริมาณ CSF ลดลง
- ปริมาณ extracellular fluid ของเนื้อสมองลดลง → brain volume ลดลง
32
etiology of increase ICP
- increase brain volume: brain edema (vasogenic vs cytotoxic)
- increase CSF volume: hydroceph
- increase intravascular blood volume: hyperemia, hypercapnea
- increase other volumes: brain tumor, hematoma
33
s&s of increase ICP
- headache esp morning, awakening pain, ปวดมากเมื่อไอจามเบ่ง
- vomiting, projectile vomiting
- eye: blurring vision, papilledema, ถ้าปล่อยให้ increase ICP ไปเรื่อย ๆ ไม่ได้รักษาจะทำให้ optic atrophy และตาบอดได้
- CN6 palsy, lateral rectus paresis
- cushing’s triad: high BP, bradycardia, abnormal respiratory pattern
- หัวโต tense fontanelle, setting sun eyes ในเด็ก
34
herniation
uncal: ipsi CN III, อัมพาตแขนขาฝั่งตรงข้าม, มาช้าอาจตายเพราะ brainstem โดนกด
- CN III compression → ipsilateral pupillary dilation
- cerebral peduncle compression → contralateral weakness and ↓level of consciousness
tonsillar: เวียนหัว หยุดหายใจ
- compression of the medulla causes life-threatening effects: respiratory arrest, cardiovascular instability, rapid loss of consciousness, often **fatal** if not treated immediately
35
tx of increase ICP
- increase brain volume: steroid → vasogenic edema, edema surround tumor / osmotic diuresis (mannitol) → cytotoxic edema, traumatic or cell ตายไรงั้นอะ
- increase CSF volume: acetazolamide for decrease CSF production, CSF diversion, แก้ภาวะ hyponat, surgery
- increase intravascular blood volume: hyperven → ↓PaCO2 → cerebral vasocon
- increase other volumes: surgical
35
รวม short q of “consciousness” ที่สั้นเกินกว่าจะทำต้อก
arousal is level / awareness is content of consciousness
36
glasgow coma scale (GCS) ~ E+M+V
[ 654 MoVE ]
- eye opening: 4) spontaneous 3) to sound 2) to pressure or pain 1) none
- best motor response: 6) obey commands 5) localizing to pain 4) normal flexion ก้คือ withdraw from pain 3) abnormal flexion 2) extension 1) none
- best verbal response: 5) orientated 4) confused 3) words 2) sounds 1) none
📰 ใช้ค่าที่ดีที่สุด & เอามาบวกกัน
37
approach to alter of consciousness
1. r/o ทุกอย่างออกก่อน ต้องมั่นใจว่าเป็น alter of conscious จริง — e.g. ptosis, lock-in syndrome, generalized rigidity แข็งทั้งตัว, aphasia, confusion, malingering แกล้งซึม
2. anatomical localization
- [COMA] brainstem: eye → downward deviate, unconjugated, skew deviate / loss of brainstem reflex → doll’s eye negative / ปวดแถวท้ายทอย
- [in BTW] bilat thalami: sleep-wake cycle disturbance
- [CONFUSE] diffuse cortical (encephalopathy ละฮะ): maybe reversible เพราะมักจะเกิดจาก toxic or metabolic
3. determine etiology
- ไม่เน้น เพราะรู้อยู่ละ vascular, trauma, infection, inflam, demyelinating, neoplastic, epileptic
- toxic cause encephalopathy: opioid, benzodiazepine, antipsychotic, antidepressant overdose
- metabolic cause encephalopathy: dysglycemia, cerebral anoxia สมองขาดออกซิเจน, CO2 narcosis, elyte imbalance, uremic encephalopathy (BUN), hepatic enceph (ammonia), myxedema coma จาก thyroid ต่ำมาก, hypertensive enceph, nutritional enceph (wernicke’s enceph)
— presence of: roving eye balls, asterixis (flap hand / frog leg), full-blown syndrome of systemic disorder, fluctuation of symptoms
— absence of: focal neuro deficit, long tract sign (babinski clonus), brainstem sign
38
brain death
- coma due to **irreversible** structural brain damage (cause ตามต้อกบน ๆ เยย)
- absence of all brainstem reflex โดยประเมิน 2 ครั้งห่างกัน 6 ชั่วโมง (pupillary light, corneal, oculocephalic ~ doll’s eye, oculovestibular ~ cold caloric, gag, cough reflex)
- apnea test positive: disconnect ventilator → CO2 level rising → still not trigger breathing bc brain already dead :(
- assess by at least 3 physician
39
nerve injury
- neurapraxia: ปลอก myelin พัง แกนปกติ — local myelin injury “conduction block”
— มีพูดถึง motor nerve conduction study (complete ตายหมด, partial ตายบางส่วน)
- axonotmesis: axon ขาด
- neurotmesis: ตัดเส้นประสาททั้งเส้น ฉับ ฉับ (neurium 3 ชั้นไปหม้ด)
40
pathophysio of nerve injury
- wallerian degen: conduction failure (จากดีแย่ เปนแย่แย่) p.15
regeneration
central chromatolysis สร้างตัวใหม่ไม่ได้เลยตาย
spontaneous activity from denervated muscle fiber → reinnervation เกิด high amp, long duration / ในพาโถเห็นเป็น fiber type grouping
- dying back axonopathy / axonal degen
length-dependent polyneuropathy (เอฟเฟคแขนขาก่อนเลย)
e.g. diabetic polyneuropathy, toxic polyneuropathy, nutritional related polyneuropathy
symptom: hypoesthesia, dysautonomia, distal muscle atrophy and weakness
- neuronopathy (w secondary axonal loss)
dorsal root ganglionopathy / sensory neuronopathy (มีอาการได้หลากหลายมาก อยากชาตรงไหนก้ชา จบ)
caused by immune (e.g. paraneoplastic dorsal root ganglionitis), intoxic, idiopathic
- segmental demyelination (ปลอกพัง→แกนพังตาม)
polyradiculoneuropathy e.g. GBS
demyelination: prolong distal latency → slow conduction velocity → abnormal CMAP (~~compound muscle action potential~~) temporal dispersion กราฟเปนเวฟเพราะความสามารถของเส้นประสาทแต่ละอันไม่เท่ากัน พังน้อย พังมาก → partial motor conduction block → total motor conduction block
41
type of NMJ disorder
- **presynaptic**
- diminish calcium ion influx at the presynaptic VGCC: LEMS, conotoxin
- defect in Ach synthesis, packaging and releasing: botulism
- **synaptic**
- Ach inh overdose: toxin → organophosphate / drug → pyridostigmine, edrophonium
- **postsynaptic**
- decreased AChR number: autoimmune (AChR-Ab) → MG / drug → neuromuscular blocking agent / toxin → bungarotoxin
42
test of NMJ disorder
- low frequency **repetitive** nerve stimulation test: กระตุ้นติดกัน 5 ครั้ง ถ้าเป็น NMJ disorder จะได้ผลเป็น decremental response
- สูตร safety factor = actual endplate potential / minimal potential required to generate action potential
- normal safety factor = 1 / minimal ≈ 10
- actual ของเราจะประมาณ 500 ปะ แต่ของคนไข้ 8 งี้ คือไม่ถึง normal safety factor
- low frequenct RNS
- MG: endplate potential ค่อย ๆ slope ลง
- LEMS: มีความ fluctuate..
43
muscle disorder ไม่เด่นไม่เน้น
symptom: weak, pain, cramp, myotonia, atrophy, hypertrophy, etc.
type
- muscle protein defect: duchenne
- muscle metabolism defect: glycogen storage disease, lipid metabo disorder
- channelopathy — ไม่เน้น
- muscle disease related to endocrine disorder: thyrotoxic myopathy (ก้ tremor ใด ๆ)
- toxic myopathy
- inflam myopathy (myositis)
- others: ischemic, trauma
44
immune response in CNS
- microglia: origin from yolk sac (not BM), MHC class II, express TLRs, กระตุ้น T cell ทำให้เกิด immune response, phagocyte and remove debris not that good, modulate immune response (for cytokine release and resolution of inflam), กระตุ้น remyelination
- CNS associated macrophages (CAMs): leptomeningeal mø, choroid plexus mø, perivascular mø → all for support and maintain barrier fx of CNS ass structure
- astrocyte: main source of CNS inflam → endothelium activation → extravasation of immune effector lymphocyte (ผ่าน BBB เข้า brain parenchyma) → ไปสนามรบ ณ ที่เชื้ออยู่ เพื่อกำจัดมัน
- adaptive immune: effector memory T cell เข้า CNS ได้บ้าง (เจอใน CSF), neuron ไม่ค่อย express MHC class I ทำให้ไม่โดน CTL ทำลาย
45
immune-mediated CNS disorders: ADEM, MS, NMO
- acute disseminated encephalomyelitis (ADEM): widespread demyelination at white matter of brain and spinal cord, anti-MOG Ig (myelin oligodendrocyte glycoprotein), after viral infection or post vaccine ADEM from molecular mimicry (e.g. rabies MMR)
- multiple sclerosis (MS): demyelinating disease (brain>spinal cord), mostly relapse and remitting ไม่หายสักกะที / acute lesion → demyelinating MS plaque, perivascular lymphocyte (CD8>CD4) / tx → IFN-β / ทดลอง experimental allergic encephalomyelopathy (EAE) แต่ไม่ได้เหมือน MS เป๊ะ
- neuromyelitis optica (NMO): ในไทยเจอบ่อยกว่า MS, demyelinating of spinal cord and optic nerve which cause paralysis and blindness / แยกจาก MS ด้วย serology → anti-AQP4 positive in NMO, also positive C’ fixation at astrocyte
- paraneoplastic disorders: anti-neuronal Ab → ต่อ intracellular component almost always ass w cancer, ต่อ cell surface Ag อาจมีหรือไม่มี cancer ก้ได้ / e.g. 50% of opsoclonus have neuroblastoma
46
immune-mediated NMJ disorders: MG, LEMS
myasthenia gravis (MG)
- mechanism: autoimmune affect postsynaptic at NMJ, neuromuscular weakness esp small m., fluctuation pattern is fatigability
- ass w thymoma: thymic hyperplasia can found in early onset MG (from active myoid muscle-like cells & APC) / cause of autoAb is thymic epith cell express Ag (e.g. AChR) → เกิด auto-reactive CD4 T cell → B cell สร้าง autoAb (anti-AChR)
- tx (focus on anti-AChR): pyridostigmine → long-acting cholinesterase inh, ไม่ได้แก้ที่สาเหตุ / thymectomy → for early-onset anti-AChR MG (elective procedure) / monoclonal Ab → eculizumab ไป target C’ เพื่อหยุด cascade, rituximab ไป target CD20 (B cell)
- drug that may exacerbate MG: aminoglycoside, quinolone, macrolide, BB, local anes, penicillamine, checkpoint inh (พวก anti-PD1, anti-CTLA4)
myasthenic syndrome of Lambert-Eaton
- Ab ต่อ Ca2+ channel at presynaptic neuron ทำให้ release ACh vesicle ได้น้อยลง (decremental response ในสภาวะปกติ)
- ทำงานดีขึ้นเมื่อถูกกระตุ้นซ้ำ ๆ at high frequency e.g. exercise จะเห็นเป็น incremental response after repetitive nerve stimulation (tetanic)
- ass w small cell lung carcinoma
- fluctuation pattern: fatigability & post-exercise facilitation
- มี autonomic dysfx ซึ่งเจอได้มากกว่า MG
47
Immune-mediated peripheral nerve disorders: GBS
Guillain-Barre syndrome (GBS)
- autoimmune demyelinating disease: proprioception loss, symmetry, weakness (+/- tingling) จากต้นขาไปแขน trunk CN
- post infectious disorder: c.jejuni (1/3 of case), M.pneumoniae, EBV, H.influ, fluA, HEV
- GBS subtype ไม่ได้สอนด้วยซ้ำาา แต่จดตามมาก่อนฮะ
- acute inflam demyelinating polyneuropathy (AIDP): sensorimotor weakness → rs muscle weakness (if late dx) / +- CN deficit +- autonomic dysfx
- acute motor axonal neuropathy (AMAN)
48
optic neuritis vs papilledema
- optic neuritis: symptom → acute vision loss, pain on eye movement / visual acuity and color vision defect / VF → central, cecocentral scotoma / affect unilateral / positive venous palsatile / cause → idiopathic, infection / refer to หมอตา
- papilledema: symptom → headache, vomiting, transient vision loss / correlated symptom → other neurological signs / VF → enlarged blind spot / affect bilateral / negative venous palsatile / cause → increase ICP / refer to หมอนิวโร 😘
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pupillary reflex test
- **light reflex**: assesses how the pupil responds to light, use to check the integrity of **optic nerve** (afferent) and **oculomotor nerve** (efferent)
- **swinging flashlight test (relative afferent pupillary defect - RAPD)**: use to identify asymmetry in the pupillary light reflex, which can indicate an optic nerve problem — e.g. from optic neuritis, glaucoma, optic neuropathy, or tumors), or a severe retinal problem (like a retinal detachment)
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head size disorder: microceph, megalenceph
**microcephaly หัวเล้ก**
- cause: mutation, zika virus, prenatal infection, toxin
- organoid model: เป็น 3D culture system mimic mini brain, used to study microcephaly
**megalencephaly spectrum หัวใหย่เกิร**
- cause: genetic mutation (PIK3CA) or metabolic disorder
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cortical structure disorder: lissen, BPH, polymicrogyria
**lissencephaly** (smooth brain bc no gyri and sulcus)
- classical lissencephaly: disruption in DCX (X-linked doublecortin), and LIS1 genes / กก development delay, epilepsy
- type II lissencephaly: cobblestone cortex (CS) / กก muscular dystrophy
**bilateral periventricular heterotopia (BPH)**
- nodular of gray matter near ventricular surface from failure of neuron to migrate
- มาด้วย epilepsy, mild intellectual disability
**bilateral polymicrogyria syndrome รอยหยักเย้อ**
- multiple small gyri with abnormal cortical lamination (คือมี excessive folder cortex w abnormal small gyri)
- มาด้วย epilepsy, developmental delay, speech problem
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injury to developing brain: WMI, CP
**cerebral white matter injury (WMI)**
- often in premature infants
- lead to motor deficit, cognitive impair
**cerebral palsy (CP)**
- group of permanent motor disorders due to non-progressive brain injury (e.g. birth asphyxia ภาวะขาดออกซิเจนของทารกแรกเกิด)
- symptom: spasticity, dyskinesia, ataxia
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genetic and congenital disorder (mental retard) : fragile X, down, fetal alcohol
**fragile X syndrome**
- FMR1 gene mutate → expansion of CGC repeat → hypermethylation and silencing of expression
- symptom: intellectual disability, autism-like, elongated face & large ear หน้ายาวหูเด่น, strabismus (crossed eyes)
**down’s syndrome**
- symptom: short stature, mid facial hypoplasia, low nasal bridge, epicanthal folds, protusion of the tongue ลิ้นจุกปาก, hyperflexibility of joints, ADHD
**fetal alcohol syndrome (FASD)**
- caused by prenatal alcohol exposure
- symptom: growth retard, facial anomalies (smooth philtrum ร่องริมฝีปากเรียบ), cognitive/behavior deficit
- first trimester → craniofacial and NTD / second trimester → neuronal generate, migrate, differentiate / third trimester → brain growth, cerebellum, hippocampus, proliferation of glial cell, development of synapse and dendrite
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learning disability (rett) and ADHD
**rett’s syndrome (ปกติ → การพัฒนาค่อย ๆ ย้อนหลัง)**
- x-linked disorder due to MECP2 mutation
- Initially normal development → followed by **loss of speech and motor skills** with hand-wringing movements
- tx: trofinetide
**Attention deficit-hyperactivity disorder (ADHD)**
- NF1 (neurofibromatosis type 1) having high incidence of LD and ADHD
- symptom: inattention, hyperactivity, impulsivity
- tx: amphetamine, methylphenidate / contrain (ทั้งสองตัวนั่น) → glaucoma, severe hypertension, arterial diseases, motor tics, and Tourette syndrome
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pathological of AD — บท neurodegen
1. Aβ aggregation → amyloid plaque (extracellular)
2. neurofibrillary tangle (intracellular)
- tau hyperphosphorylation
- normal tau: assembly and stabilize microtubule / alzheimer มีเท่า ๆ normal ppl
- P-tau (phospho-tau): inh microtubule assembly / alzheimer มีเยอะกว่าคนปกติ (ไอ seeding หาพวก โรคแพร่กระจาย ของบท dementia syndrome)
- tau mutation: cause familial frontotemporal dementia / ไม่ทำให้เกิด AD **
- neuronal loss → พอ decompensate เลยเกิด dementia ซึ่งแต่ละคนมี resilient threshold ต่างกัน “amnestic multidomain dementia”
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genetic in AD
≤5% familial AD มักจะ early-onset (<65yo)
- presenilin 1, 2 (PSEN1, PSEN2): เป็น autosomal dominant, component of γ secretase ****กก.การ cleave ไรงั้น, missense mutation at 8-TMD ถือว่าเป็น most aggressive AD
- amyloid precursor protein (APP): chromosome 21 ass w down, mutation in APP cluster at β secretase cleavage site เหมือนพอตัดผิดที่ก็เลยมี Aβ↑↑
sporadic ~ multifactorial
- apolipoprotein E4 (ApoE4): late-onset familial & sporadic AD, express in astrocyte and microglia
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classic sequence of AD
- papez circuit dysfx: episodic memory loss → repetitively telling old story, cant register new memory [เพราะ tau ชอบมา mesial-temporal แถว ๆ entorrhinal cortex]
- frontal cortex dysfx: executive dysfx ทำสิ่งที่เคยทำประจำไม่ได้, self-dependent behavior นิสัยเหมือนเด็ก
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tx of AD
- cholinesterase inh
- may improve cognitive score
- mild-moderate AD: donepezil, rivastigmine, balanthamine
- NMDA receptor modulator (เป็น glutamine receptor นะเผื่อลืม)
- mod-severe AD: memantine
- monoclonal Ab
- aducanumab: ลด Aβ plaque, อาจไม่ improve cognitive fx (just clinical meaningful? ARIA amyloid-related imaging abnormalities)
- lecanemab: early tx slow cognitive decline
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huntington — บท neurodegen
- mutation of huntingtin gene (chromosome4)
- CAG repeat at coding region → ได้สาย polyglutamine (ซึ่งท้อกซิกก)
- mutant polyglutamine protein → neuronal inclusion คือ neuron breakdown เลย atrophy (at striatum hippocampus cerebellum)
- รุ่นลูกจะยิ่ง repeat ยาวขึ้นเรื่อย ๆ “gene instability” → อาการหนักขึ้น และ onset เร็วขึ้น → disease anticipation
- clinical manifest: motor defect → chorea or loss of coordination / dementia / psychiatric
- tx: VMAT inh (tetrabenazine and reserpine) ใช้ทรีตพวก chorea ass w huntington โดยจะลดการดึง dopamine เข้า synaptic vesicle
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motor neuron ALS (Amyotrophic lateral sclerosis)
- SOD1-mediated toxicity in ALS is not due to loss of function
but instead to a gain of one or more toxic properties that are independent of the levels of SOD1 activity
- TAR-DNA binding protein TDP-43 ≈3-4% of fALS
- TARDBP mutation has been identified in 1.5% of sALS
- C9ORF72 repeat 32% of fALS, 25.9% FTD
tx
- riluzole inh glutamate release (block voltage-gated Na channel)
- radicava: reduce oxidative stress
- tofersen: target SOD1
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definition (?) of neurogenetics
- one gene affect more than one localization: C9orf72 ทำให้เกิดได้ทั้ง ALS & FTD ขึ้นกับสเปกตรัมแต่ละคน
- one gene can lead to various disease: homozygous GBA lead to gaucher while heterozygous lead to parkinson
- mutation in different gene can result in same disease: in AD มันก้เปนกลไกรวม ๆ เนอะ พังจุดนึงก้เอฟเฟคหมด แค่นั้นแหลเ
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neurogenetic x neurodegenerative disorders
- huntington’s disease (HD): HTT mutate → expansion of CAG trinucleotide repeat (also can be penta or hexa)
- spinocerebellar ataxias (SCA)
- alzheimer’s disease (AD): APOE4, also APP PSEN1 PSEN2
- parkinson’s disease (PD): GBA mutate common in TH
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neurogenetic x neuromuscular disorders
- duchenne muscular dystrophy (DMD): mutation of dystrophin gene on X chromosome / เป็น x-linked recessive / tx: axon skipping, AAV-mediated gene transfer, CRISPR/Cas9 in gene editing
- spinal muscular atrophy (SMA): mutation of SMN gene on chromosome 5 / AR / ant horn cell degen → skeletal muscle atrophy
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neurogenetic x neurocutaneous disorders จำรูป จำนิยาม
- neurofibromatosis (NF) 1: NF1 mutate on chromosome 17 ซึ่งพอ mutate จะได้ neurofibromin มาแทน / neural → optic pathway glioma, brainstem glioma, lisch nodule (ในตานี่นับเปนนิวโรมั้ย) / skin → cafe au lait, axillary freckling
- neurofibromatosis (NF) 2: NF2 mutate on chromosome 22 / neural → acoustic schwannomas, meningiomas / skin → subcu schwannoma ปูดเลยอะ ทุเร่ดมากㅠ.ㅠ, NF2 plaque
- tuberous sclerosis (TS): TSC1 mutate on chromosome 9 OR TSC2 mutate on chromosome 16 / neural → tuber, subependymal nodule (SEN), subependymal giant cell astrocytoma (SEGA) / skin → ash leaf, shagreen, periungual fibroma (koenen’s tumor), adenoma sebaceum — คนไข้มักมาด้วยชักเพราะ tumor ในสมอง
- sturge-weber syndrome (SWS): sporadic / neural → leptomeningeal angiomatosis (calcification + atrophy) / skin → port-wine stain เหมือนราดไวน์บนหน้า
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neurogenetic x neurodevelopmental disorders
- open NTDs: spina bifida (myelomeningocele), anencephaly
- factors ที่เกี่ยวกับ NTDs
- environment: maternal folate def, maternal exposure to valproate
- genetic: methylenetetrahydrofolate reductase (MTHFR) polymorphism เพราะทำให้ impair folate metabolism = turn to active form น้อยลง ;(
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cortico-striato-pallido-thalamocortical circuit ที่จะสื่อคือ pd pt ก็เป็นหมดนี่แหละ both motor and non-motor loey
1. nigrostriatal pathway (motor loop): motor cortex → putamen → lateral GPi → ventral lateral nuc. พอลูปพังเลยเกิด movement disorder
2. mesocortical pathway (executive loop): dorsolateral prefrontal cortex → dorsolateral caudate → medial GPi → medial dorsal and ventral anterior nuc. พอลูปพังเลยเกิด cognitive disorder
3. mesolimbic pathway (limbic loop): anterior cingulate cortex → ventral striatum → ventral pallidum → medial dorsal nuc. พอลูปพังเลยเกิด neuropsychiatric disorder
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internal circuit of basal ganglia
1. direct: ↑ Cortex stimulation → ↑ Striatum (D1 receptors) → ↓ GPi/SNr inhibition → ↑ Thalamus activity (VL) → ↑ Cortex activity → Facilitates movement
2. indirect: ↑ Cortex stimulation → ↑ Striatum (D2 receptors) → ↑ GPe inhibition → ↓ STN activity → ↓ GPi/SNr inhibition → ↓ Thalamus activity (VL) → ↓ Cortex activity → Inhibits movement
3. hyperdirect: ↑ Cortex stimulation → ↑ STN activation → ↑ GPi/SNr inhibition → ↓ Thalamus activity → ↓ Cortex activity → Rapid movement suppression
p.s. STN = subthalamic nuc, SNr = substantia nigra reticulata, SNc = substantia nigra compacta
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parkinsonism and basic info of pd บท movement disorder
**parkinsonism**: symptom including bradykinesia, rigidity, resting tremor, loss of postural reflex, flexed posture, freezing
**parkinson’s disease**
- pathologic: extranigral PD pathology during prodromal pd → nigral PD pathology during clinical dx
- braak stage & caudal-rostral spread
- risk factor: modify → pesticide, daily product, traumatic brain injury พวกนักมวย / non-modify → older age, male, having family hx
- protective factor: coffee (ปริมาณเยอะ), black tea, mediterranean diet, physical activity, good sleep
- pathophysio: direct ลด indirect เพิ่ม = hypokinesia
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clinical pd บท movement disorder
- clinical dx ปกติไดแอกจากอาการเป็นหลัก: parkinsonism, exclude other cause of parkinsonism, have supportive feature (e.g. unilat or asymmetry onset, resting tremor, response to levodopa, levodopa induced dyskinesia, chronic progressive disorder
- pattern of brainstem degen อาการเป็นยังไงก็ขึ้นกับส่วนของสมองที่เป็น
- red flag for atyp parkinsonism: rapid progression, poor response to levodopa
- drug-induced vs PD: sym vs asym / subacute vs chronic progress / concurrent orofacial dyskinesia vs nothing [e.g. haloperidol, antiemetic
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tremor
- essential tremor → kinetic>postural, hand head voice jaw, similar frequence / essential physiologic → hand finger, increase w stress exercise fatigue caffeine thyroid, decrease frequency > 1Hz
- essential tremor → sym, alcohol responsive in young-onset / parkinson tremor → pill rolling, rarely head tremor
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myoclonus
ดูลักษณะที่กระตุกจะบอก lesion ได้เลย
- cortical: shock-like, postural or movement, irregular but often rhythmic, generalized ~ **distal** extremity
- subcortical: less shock-like, เป็น at rest, periodic, axial (**cranial** and proximal extremity) // caused by post-hypoxic, metabolic, toxic, drug
- spinal: can be shock-like, at rest, periodic or rhythmic, **axial** (NO cranial and face)
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chorea
- primary (hereditary): autosomal dominant → huntington or huntington-like / autosomal recessive → neuro-acanthocytosis, wilson / x-linked recessive → McLeod, Lesch nylhan
- secondary: drug → antipsychotic, levodopa, AED, steroid / metabolic → hypergly, dysNa, hypoCa, hypoMg, hyperthyroid, hypoPTH, vitB1 or B12 def / infection → relapse HSV / autoimmune → sydenham’s chorea, anti-NMDA, anti-BG, SLE, APS, paraneoplastic / vascular → ischemic or hemorrhage, PV, moya moya disease, post pump chorea / hormone → chorea gravidarum
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tics ~ tourette’s syndrome
มีทั้งขา motor และ vocal
kw !
- copropraxia: obscene gesture แย่ ไม่เหมาะสม
- echopraxia: copy movement ทำตามคนอื่น
- coprolalia: obscene word พูดคำแย่ ๆ
- echolalia: copy word
- palipalia: repetition same phrase word or syllable
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dystonia
- etiology: acquire → perinatal injury, brain injury, drug, toxic, vascular, tumor, infection / inherited / idiopathic
- clinical manifest: sustain muscle contraction, abnormal posture (slow twisting), repetitive movement (jerk or irregular but pattern), triggered by action, overflow to adjacent muscle, presence of sensory tricks
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multimodal analgesia
- การใช้ยาแก้ปวด 2 ตัว+ (action คนละแบบ) เพื่อเสริมฤทธิ์กัน จะได้ลดโดสและ ADR ของแต่ละตัว
ขอทวนให้เร้กน้อยว่าแต่ละจุด มียาไหนมาออกฤทธิ์ได้บ้าง
- transduction: NSAID, COX-2 inh, topical local anesthetics
- transmission: epidural block, regional anesthesia
- modulation: COX-2 inh, α2 ago, **opioid**, ketamine
- perception: **opioid**, ketamine, α2 ago
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opioid ~ overview
- receptor: full agonist → morphine, oxycodone, methadone, hydromorphone, heroin / partial agonist → buprenorphine / antagonist (จับแน่นกว่า ago, เฆี่ยน ago แล้วไปจับแทน) → naloxone, naltrexone / ago-anta (เข้าไปเฉย ๆ จะออกฤทธิ์ ago, ถ้าก่อนหน้าให้ ago จะออกฤทธิ์ anta) → nalbuphine, pentazocine
- ADR of opioid: sedation, rs depression, meiosis, euphoria, placenta transfer, inh gut motility, sphincter of oddi spasm
- risk factor of respiratory depression from opioid: extreme age เด่กหรือแก่เกิน, hx of sleep apnea, COPD, hepatic dysfx, renal dysfx
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opioid แยกรายตัว
- codeine: natural and weak opioid, CYP2D6 ตัวเดียวกับ quinidine, o-demethylation แล้วจะกลายร่างเปน morphine
- tramadol: increase potency by acetaminophen, CYP2D6, ADR → nausea
- morphine: morphine โดน uridine glucoronosyl transferase (UGT) ได้ **M3G** (no affinity, induce allodynia and hyperalgesia) & M6G (more potent than morphine!! ซึ่งสลายช้ากว่า morphine อี้ก) / paradoxical pain in M3G ให้ยาแทนที่จะหายแต่ดันปวดกว่าเดิม แก้ด้วยให้ opioid ตัวอื่น
- pethidine (meperidine): less potent than morphine 10 เท่า, can tx shivering สั่นกึก ๆ, use as local anesthetic / demethylation in liver ได้ norpethidine ซึ่งท้อกซิก ทำให้เกิด anxiety, mood change, tremor, seizure
- fentanyl: 80-100 more potent than morphine, highly lipophilic and bind strongly to plasma protein เลยมักใช้ในรูป transdermal or transmucosal / ใด ๆ คือ short duration นะเพราะ tissue uptake ไวจั๊ด / fentanyl dealkylation in liver (CYP3A4) ได้ norfentanyl ซึ่งเซฟต่อไต
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propofol (anesthesia)
action (?)
- CNS: CNS depression, neuroprotective, anticonvulsant, CMRO2↓, cerebral blood flow↓, ICP↓, euphoria
- CVS (BP droppp): peripheral vascular resistance↓, stroke volume↓, CO↓
- RS: rs depression, bronchodi
- GI: antiemetic (เมื่อใช้น้อย ๆ ไม่ถึงกับสลบ)
clinical use
- general anes: induction, maintenance
- conscious and sleep sedation
- postoperative n/v prophylaxis
- อย่าใช้สำหรับยานอนหลับหรือ euphoria ❌
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acute bacterial meningitis (prognosis, pathogen)
- meningitis identified by CSF pleocytosis (wbc>5cell/mm3)
- prognosis: high mortality rate (up to 20%), severe sequelae
- pathogen and susceptible age: under 1mo → S.agalactiae, E.coli, L.mono / 2-50yo → S.pneumo, N.mening / over 60yo → S.pneumo, N.mening, L.mono
- pathogen and predisposing factor: asplenia → S.pneumo, H.influ, N.mening / C’ def → N.mening / cell-immediated immune defect or HIV or steroid use → L.mono, NTS / mother-to-child in utero or during delivery → S.agalactiae, L.mono / base skull fracture or CSF leak → S.pneumo / head trauma or after neurosurgery (contam) → S.aureus, coagulase-negative-staph, aerobic gram-neg e.g. pseudomonas / CSF indwelling shunt → S.aureus, coagulase-negative-staph, aerobic gram-neg e.g. pseudomonas, C.acne / undercooked pig → S.suis / contam food (cold meet or ผักผลไม้นมชีส) → L.mono เพราะเป็น foodborne
- vaccine ไปดูไว้ให้พอผ่านตา
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acute bac meningitis (pathogenesis, clinical presentation)
**pathogenesis เดะกลับมาพิม**
- mucosal colonization
- intravascular vs intracellular survival
- meningeal invasion
- immune response in subarachnoid space
**clinical presentation**
- classic triad: fever, nuchal rigidity (meningismus), altered mental status
- based on age: เด่กมากอาการอาจ nonspecific งอแง ไม่กินข้าว ง่วง ไข้ขึ้น / แก่มากอาจมาด้วย fever sepsis hemiparesis seizure coma ไปเลยก้ได้
- based on pathogen
- N.mening → purpura fulminans which can lead to gangrene, มีวัคซีนป้องกันแต่ไม่ได้อยู่ใน routine
- L.mono → granulomatous nodular skin rash / cause invasive listeriosis ได้ด้วย rhombencephalitis งี้ ถ้า infect in neonate ก้อาจเกิด abortion, prematurity, neonatal sepsis
- based on duration: increase ICP, reduced level of consciousness → intracranial complication e.g. subdural effusion/empyema → extracranial complication e.g. SIADH → long term sequelae e.g. sensorineural hearing loss, epilepsy, hydrocephalus
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acute bac meningitis (invest, ABX)
investigation
- hemoculture → always do first before give ABX / LP → should be done if no contrain and also before ABX / brain imaging → not for dx, CT brain before LP if suspected intracranial mass or ICP↑
- แปลผล CSF in infectious meningitis: bac → protein สูง glucose ต่ำ PMN / TB → protein สูงมาก glucose ต่ำ MN / viral → ใกล้เคียง normal, MN / cryptococcal → protein สูง glucose ต่ำ MN
ABX
- golden period<6hrs / ตารางเชื้อไหนให้ยากี่วัน ยาไร น่าจะไม่ออก?
- adjunct steroid therapy: use in S.pneumo & H.influ type B / 20mins before or concurrent w first dose of ABX
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tuberculous meningitis
- pathogenesis: block ทางเดิน CSF lead to ICP↑ → obliterative vasculitis lead to brain ischemia → perineuritis result in CN palsy → direct parenchymal involve
- epidemiology: ใน high prevalence area → ส่วนมากเป็นเด็ก<5yo / low prevalence → ส่วนมากเป็น adult w HIV
- clinical presentation: ช่วงแรกไม่ค่อยมีไร แต่ถ้าไปสมองจะ prominent meningeal signs, altered mental status, stroke, hydrocephalus, and CN palsy
- contrast CT (4 pattern): basilar arachnoiditis, tuberculoma, cerebral infarction, hydrocephalus
- tx ~ regimen ที่เคยเรียนกับอ.นพดลไปแย้ว, adjunct steroid เสมอ
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brain abscess
- pathologic process: เน้นวันที่ 10-13 จะเห็น ring-enhancing capsule on imaging
- pathogenesis: contiguous spread from parameningeal foci (มาจากคนใกล้เคียง หู ไซนัส ฯลฯ) , hematogenous spread (พวก cyanotic congenital heart disease มีโอกาสเป็นง่ายขึ้น) , head trauma or after neurosurgery
- pathogen in: immunocompetent → strep, enterobacteriaceae, anaerobe, S.aureus / immunocompromise → nocardia, toxoplasma, candida, cryptococcus, aspergillus
- clinical presentation: classic triad เดิม, อาจเกิด neurologic sign แถว abscess
- investigation: never LP
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poliovirus
- transmission: faeco-oral route
- pathogenesis
- replicate in gut wall then mostly secrete into feces = asymptomatic
- if some migrate to tonsil or peyer’s patch then go to RE system = viremia “acute febrile illness” //ที่น่าสนใจคือวัคซีน cant crossing into vss ทำให้เราไม่ติดเชื้อแน่ ๆ
- viremia → retrograde axonal transport from NMJ to CNS (cause polio enceph and polio mening)
viremia → direct invasion through BBB (cause aseptic mening) to CNS (cause polio enceph and polio mening)
- clinical manifest: mostly asym → acute febrile illness (abortive poliomyelitis) → aseptic mening (nonparalytic poliomyelitis) → **paralytic poliomening** → polioenceph (rare)
- paralytic poliomening: primarily affect ant horn cell, asymmetrical, lower>upper limb / classic case → **rapid progressive paralysis of one leg w LMN sign**
- OPV (oral polio vaccine): live attenuated, provides gut immunity and interrupt transmission, rare risk of circulated vaccine-derived poliovirus (VDPV) and vaccine-ass paralytic polio (VAPP)
IPV (inactivated): no risk of cVDPV and VAPPbut less effective for herd immunity
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enterovirus 71 (EV71)
- basic info: hand foot mouth disease (coxsackie A16 most common, but EV71 is more severe)
- disease: self-limited fever, malaise, sore throat, painful oral exanthem & enanthem, papulovesicular rash at palm and sole [มักเกิดในเด็ก 5-7 yrs & recovery in 7-10 days]
- neurological manifest เรียงตามความ common
1. brainstem encephalitis: myoclonus, ataxia, nystagmus, oculomotor palsies, bulbar palsy / occasionally induce autonomic dysfx like fluctuating BP, pulmonary hemorrhage
2. aseptic meningitis: ใช้แค่ clinical แยกจาก other aseptic meningitis ไม่ได้
3. acute flaccid paralysis: คล้าย poliomyelitis แต่ better recovery rate
- dx: **RT-PCR** → **ตรวจจาก CSF ไม่เจอ** เพราะมักจะอยู่ที่ throat, stool, and maybe skin-vesicle fluid / **brain MRI** จะเจอ brainstem enceph
- vaccine: still in phase IV clinical trial in china
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rabies virus ੯‧̀͡u\🐾 ถ้าอาการมาแล้วก็ incurable นะฮับ
- pathogenesis: virus enter via wound (animal bite) → replicate in muscle → travel retrograde axonal to CNS via peripheral nerve → reach brain → massive replication occur กระทบสมองหลายส่วน
- **negri body**: cytoplasmic inclusion consisted of accumulated rabies RNA which prominently found in pyramidal cells
- clinical manifest
1. prodrome: specific → itching or paraesthesia at bitten site / non-specific → fever, headache, myalgia, fatigue, anxiety, insomnia
2. furious: hydrophobia, aerophobia, hyperactivity, aggression, spasm, fluctuation of consciousness, lacrimation, salivation [death in 1wk after onset]
3. paralytic/dumb: hypotonic weakness or paraesthesia at bitten site → constipation, urinary retention, respiratory failure [death in 1-3wks after onset]
- management: aggressive washing w soap and running water >5 mins / swab w virucidal agent e.g. povidone iodine or 70% alcohol / ABX to prevent 2˚ bacterial infection e.g. P. multocida / tetanus vaccine (dT or TdaP) / immunisation (active ± passive)
- classification: I) แตะ ๆ → no tx needed / II) แผลเล็ก ๆ → vaccinate / III) แผลและเลือด → vaccinate and RIG if needed ฉีดรอบแผลให้มากที่สุดเพื่อ neutralized เชื้อไม่ให้ไปไหน
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japanese encephalitis virus (JEV)
- transmission: vector → culex mosquitoes ยุงรำคาญ / amplifying host → pig, wading birds
- pathogenesis: mosquito bite site → JEV replicate in langerhans cell, mΦ, fibroblast, endothelial cell → viremia
- clinical manifest: **encephalitis** (<1%) ****∼ AoC, headache, vomit, convulsion esp children / **EPS** (1/3 of children): flat **mask-like facies** w wide unblinking eye, tremor, generalised hypertonia, cogwheel rigidity
- dx: anti-JEV IgM in CSF or serum (ตรวจได้ 3-8 days after onset) / CSF profile shown lymphocytic pleocytosis / MRI found lesions in thalamus and/or basal ganglion / **RT-PCR not recommend** มันตรวจบ่ขึ้นค่า
- live-attenuated vaccine
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zika virus
- transmission: mosquito (Aedes), vertical (mother-to-fetus), sexual contact
- symptom are generally mild and non-specific: rash, fever, conjunctivitis, arthralgia, malaise, headache → confirm w lab
- congenital zika syndrome: microcephaly, limb contracture, high muscle tone, hearing loss
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mumps virus — ไม่เจอมา 5 ปีแว้ว
- respiratory droplets → local replication in upper rs tract → viremia → pancreas, gonads, myocardium, breast, kidneys, CNS
- 5-10% meningitis: acute aseptic meningitis w or wo parotitis
- <0.5% encephalitis: acute encephalitis and may found hearing loss and nystagmus
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measles
- มาด้วย generalized maculopapular rash. two weeks after the rash resolves, he develops seizures and confusion. MRI shows demyelination ชั้นจดอะไรมา555555555555
- CNS involvement
1. acute measles encephalitis (concurrent w/ rash)
2. acute disseminated encephalomyelitis (**ADEM**): occur a few weeks after rash resolves, autoimmune demyelination, **tx w high-dose steroid**
3. subacute measles encephalitis: several month after acute illness, lethargy, confusion, seizure, myoclonus in immunocompromise
4. subacute sclerosing panencephalitis (SSPE): rare, chronic demyelinating disease,
- MMR accine: prevents measles, mumps, rubella
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herpes simplex
- clinical features: fever, confusion, seizures, temporal lobe involvement (personality changes or hallucination)
- investigation: PCR for HSV in CSF >90% sensitivity and almost 100% specificity
- tx: give aciclovir ASAP
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angiostrongylus cantonensis (rat lungworm) 🐌🐀
- morpho: adult female have coiled patterns (twisting together of the intestine and uterine tubes)
- habitat: pulmonary a. of rat
- host: DH → rodent / IH → snail, slug / paratenic host → shrimp, crab, frog, monitors / AH → human
- life cycle: หนูขี้ 1st larva ละหอยกินเข้าไป → โตเป็น 3rd ในหอย → หนูกินหอยที่มี 3rd larva → 3rd penetrate from intestine to bloodstream → 3rd move to CNS ละกลายเป็น sub-adult → กลับไป bloodstream เพื่อ mature in Rt ventricle & pulmonary a. → female lay egg และ egg hatch to 1st → 1st penetrate alveoli and move to trachea → หนูสำลักและกลืน 1st เลยไปอยู่ในขี้
- mode of infection: ingest food that contain 3rd larvae
- mode of transmission: food-borne transmission
- infective stage: 3rd stage larvae
- dx stage: 3rd stage larvae in CSF (most are negative)
- disease: cerebral angiostrongyliasis, eosinophilic meningitis, eosinophilic meningoencephalitis
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host species
- DH → rodent (หนูท่อ rattus norvegicus, หนูท้องขาว rattis rattus, หนูพุกใหญ่ bandicota indica)
- IH → snail (หอยทากลาย achatina fulica, หอยโข่ง pila spp., หอยขม sinotiana martensiana) / slug (varonicella alte, varonicella siamensis)
- paratenic host → shrimp, crab, frog, ตะกวด monitors
- AH → human
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angiostrongylus clinical
- incubation 1-3wks / symptom last 2-6wks
- clinical manifest: like bacterial meningitis ~ excruciating headache, neck stiffness, n/v, abnormal sensation of limb, serious complication but rare is neurodysfx
- patho finding: eosinophilia meningitis → tortuous track of various size in brain and spinal cord surrounded by inflam reaction and degen neuron → granulomatous response to dead parasite → non-specific vascular reaction e.g. thrombosis, vss rupture, arteritis, aneurysm formation
- lab finding
- CSF: pressure above 200 mmH2O, opalescent or turbid but not purulent, leukocyte 500-2000 which have 25-75% of eo (pleocytosis), elevated protein, normal or slightly reduced glucose
- CBC: leukocytosis w eosinophilia
- imaging
- CT: cerebral edema, ventricular dilate, ring enhancing or disc lesion, resembling tuberculomas
- MRI can be normal: leptomeningeal enhancement, hyperintense on T2, nodular gadolinium enhanced lesion on T1
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angiostrongylus dx & tx
- dx: hx taking and clinical presentation**, CBC CSF finding ~ elevated eosinophil, ELISA (Ab detection in chronic), PCR (Ag detection in acute) / definite is larva from CSF, CNS, ocular chamber, autopsy
- tx: no specific tx / supportive tx → LP release pressure, analgesia, steroid therapy / antihelminthic still controversy
- prognosis: benign and self-limiting, severity based on number of larvae ingested, mortality rate is lowww
- prevention: health edu, proper cook of mollusk prawn crab, proper washing vegetable, rodent eradication (ยาก)
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patho of brain tumor ทุกโรค55555555
- pilocytic astrocytoma: at cerebellar midline / micro → cell process เยอะ คล้ายเส้นผม, **rosenthal fiber**
- low-grade diffuse astrocytoma: eccentric nuc. คล้าย reactive astrocyte มาก ๆ, mass effect, infiltrative border
- glioblastoma (GBM): most malignant tumor of astrocyte / gross → **hemorrhage**, necrosis, butterfly lesion (ข้าม corpus callosum) / micro → pseudopalisading necrosis เซลล์เรียงตัวรอบเนื้อตาย, microvascular proliferation, eccentric nuc + red cytoplasm + glial process ดูแล้วจะคล้าย ๆ astrocytoma
- oligodendroglioma: infiltrative border, round cell w perinuclear halo
- choroid plexus papilloma: gross → **cauliflower mass** at ventricles / micro → **papillary pattern** มี fibrovascular core
- ganglioglioma: มักเกิดที่ temporal lobe คนไข้มาด้วยชัก, solid cystic mass / micro → binucleate neuron (ganglion cell) + glial cell
- medulloblastoma: common in child, from cerebellar stem cell, highly malig / micro → round cell, chromatin เข้ม, hyperchromatic nuclei, frequent mitosis, **homer wright rosette**
- meningioma: extra-axial tumor ติด dura กดเจ็บ, อาจเกิดแถว ๆ ventricle (จาก choroid plexus) หรือ optic n. ก็ได้ / micro → oval nuc, vesicular chromatin, whorl arrangement or sheet-like, syncytial appearance คือเห็น cytoplasm แยกกันไม่ชัดเจน, psammoma body (calcified structure)
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primary brain and other CNS tumors
- meningioma
- extra-axial หมาอยู่ใต้พรม vs intra-axial เต่าอยู่บนโต๊ะ
- neurofibromatosis type 2 (NF2): have many meningioma
- tumors of pituitary
- micro → <10mm, prolactinoma is most common / macroadenoma → >10mm, cause bitem hemianopia
- nerve sheath tumor (schwannoma)
e.g. bilateral vestibular schwannoma in NF2 pt (acoustic neuroma)
💡 which cause primary brain tumor?: **genetic mutation** (risk factor include genetic predisposition of cancer syndrome, prior radiation exposure, HIV)
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clinical presentation
- direct neurological deficit: tumor itself, surrounding vasogenic edema
- pain (headache): traction force (on meninges or large vss)
- seizure: irritation to cortical neurons
- false localizing signs: distortion of structure
- CN6 palsy จุดต่ำสุดก้งี้ โดนทับตลอด
- kernohan’s notch phenomenon: cause ipsi motor deficit (เลยอาจถูกตีความผิด)
- arterial/venous infarction: vascular compression or invasion
- bleeding tumor: vascular invasion, abnormal vss เหมือนรีบสร้างเกินเลยอ่อนแอ
- increased ICP: direct mass effect อุดทางเดิน CSF งี้, ventricular obstruction, venous sinus occlusion //พวก clinical manifest of ICP↑ ตามเลคนั้นเยย
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cancer neurology - paraneoplastic syndrome, ADR of cancer therapy
- paraneoplastic neurological syndrome //cancer สร้าง autoAb → attack neuro ทำให้เกิดโรค
- LEMS → SCLC
- dermatomyositis (DM) → CA breast lung ovary etc.
- ADR of chemotherapeutic agent: area postrema syndrome อ้วกก, length-dependent polyneuropathies
- ADR of radiation therapy (delayed onset หลายเดือนค่อยเกิด): radiation necrosis of brain parenchyma, cranial neuropathies
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headache mechanism 4 แบบ
1. vascular: pain located depend on affected vss, +/- throbbing
2. meningeal: mechanical force → mass, increased ICP / chemical irritation → diffused headache esp แถว orbito+temporal+occipital, อาจมาพร้อม n/v ได้
3. cranial neuralgia ไฟไหม้ ไฟช๊อต: neuropathic pain, ตาม dermatome
4. pain from paracranial structure (~referral pain): ปวดไซนัสกระจายไปส่วนต่าง ๆ ,etiology at base of skull จะปวดขมับขนาดเท่าเหรียญบาท
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primary headache: migraine basic info and tx
- clinical manifest รวม ๆ
- headache: orbito-temporal-occipital เพราะไปกระตุ้น meninges, unilat or bilat แต่จะมีข้างที่เด่นกว่า, throbbing and plsating, episodic (ซึ่งจะ lasting ≈ 4-72hrs)
- n/v
- photophobia, phonophobia
- phase: premonitory → **aura** → headache → resolution
**aura** อาจมีหรือไม่มีก้ได้ แต่ถ้ามีก้ (p.s. visual aura: scintillating-scotoma เกิดสปาร์กกิ้งวิ้ง ๆ ละตาบอดชั่วขณะ / somatosensory aura: cheiro-oral numbness ชาจากปลายมือสู่ปาก)
- related kw: MOH medication overuse headache / migraine chronofication ไมเกรนแอทแทคบ่อย หรือไม่หายเลย / nociplastic pain ตอบสนองกับสิ่งที่ไม่ควรจะ pain เช่นการขยับหัวไปมา
**tx**
- abortive medication
- ไม่เด่นไม่ดัง NSAIDs and COX-2 inh / ergotamines: ADR ischemia from vasocon
- 5HT(1B/1D) ago [-triptan]: inh neuropeptide, ลด cellular cAMP, เพิ่ม vasocon, ADR CVS risk
- CGRP receptor monoclonal Ab: ใช้ดีในปัจจุบัน
- dopamine anta: blocks DA in hypothalamus ไม่ให้ไปกระตุ้น trigeminal nociceptive system
- preventive medication
- TCAs (amitriptyline, nortriptyline): increase synaptic 5HT & NE, stimulate alpha-2 receptor //low dose TCAs is recommend :)☆
- BB (propanolol, metoprolol): ลดถี่ ลดความรุนแรง inh inducible NOS
- antiepileptic (valproate, topiramate): blocks excitatory ion channel, facilitates GABA neurotransmission
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primary headache: migraine but PATHOPHYSIOOO
1. **triggers and cortical spreading depression (CSD):** stress, light, sleep disturbances activate susceptible brain regions → เกิด CSD เปนเหมือน wave of neuronal depolarization spread across cortex ซึ่ง ass w aura symptom → activates trigeminal system
2. **trigeminal system activation:** trigeminal ganglion (**TG**) → activated by signal from CSD or brainstem nuclei, release neuropeptide like CGRP PACAP SP NK / trigeminal nucleus caudalis (**TNC**) → central relay for pain signal from head and neck, modulate pain signal / trigeminal cervical complex (**TCC**) **→** send signal to thalamus
3. **neurogenic inflammation: CGRP →** vasodilation and sensitization of pain pathway / **PACAP →** nociception and vasodi / **SP →** promotes inflam
4. **parasympathetic activation** (SSN-SPG circuit): trigeminal system activate **SSN** then SSN activate **SPG** → SPG release **VIP** **NO NPY**, causing cranial vasodi and autonomic symptom (e.g. tearing, nasal congestion)
5. **central sensitization (thalamus):** process pain signal from TNC and prolonged activation lead to central sensitization — heightened pain sensitivity, allodynia (pain from non-painful stimuli)
ซึ่งด้านบนเน้นเปน migraine w aura แต่จริง ๆ เราเชื่อกันว่า migraine w/o aura อาจเริ่มต้นจากทั้งสองข้อนี้ ละไป activate trigeminal nociceptive system อีกที
- **hypothalamic disturbance** enhance craniovascular and meningovascular parasym tone
- **inadequate pain modulator**: dysfunction in **PAG** (กก endogenous opioid) **LC** (กก NE) **RN** (กก 5-HT) lead to insufficient **descending inhibition** of ascending nociceptive signal → pain from peripheral trigeminal fiber is amplified and perceived more intensely
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primary headache: tension-type headache (TTH)
- band-like headache ปวดเหมือนมีไรรัดหัว จาก temporalis m. ตึง
- +/- myofascial pain syndrome (MPS)
- อาการปวดมากขึ้นตอนบ่าย ๆ เย็น ๆ
- tx: paracetamol, NSAIDs, COX-2 inh / ถ้าเป็น migraine ด้วยให้ tx w TCAs
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primary headache: trigeminal autonomic cephalalgias (TACs)
- โรค prototype: cluster headache
- ปวดตอนนอนจนตื่นขึ้นมาได้ / ใช่ที่ปวดเวลาเดิมเป๊ะ แต่เว้นห่างไปเปนปีได้เลยไรงั้นปะะะ
- pathogenesis คล้าย migraine
- ปวดเด่นบริเวณตา ข้างเดียว no alternating - ครั้งละ 1-2 hr
- มีน้ำมูกไหล นํ้าตาไหล ‘dysautonomia’
- tx: 100% O2
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reflex syncope
step 1
- predisposing condition (e.g. dehydrate, peripheral vasodi) → venous return↓ → baro reflex activate ทำให้ sym↑ parasym↓
step 2
- แต่มีเหตุการณ์ (e.g. urination, defecation, cough, etc) เข้ามาทำให้ sym↓ parasym↑ (ตรงข้ามกับ baso)
- can be caused by fear or anxiety → mismatch ventricular fill & contraction called “empty ventricle” → stimulate ventricular mechanoreceptor
step 3
- result: sym↓ parasym↑ → bradycardia syncope
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symptom of syncope
- presyncopal symptom: lightheadedness, palpitation, visual
disturbances — ซึ่งถ้าเราลด predisposing factor ทันก้จะไม่เกิด syncope
- during event: TLOC (วินาที), cold & pale skin, neuro symptom (urine/fecal incontinence, tonic/clonic limb movement)
- rapid recovery w/o neuro deficit
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seizure vs syncope
preictal period
- มี aura / มี lightheadedness, nausea, diaphoresis, tunneling of vision
- transition to unconscious: immediate / ≈second
ictal period (during seizure)
- duration: minute / second
- duration of tonic or clonic movement: 30-60s / <15s
- appearance: cyanosis, frothing at mouth / cold & pale
postictal period
- confusion and sleepiness after event: minute to hrs / <5mins
- aching of muscle: **often** / sometimes
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normal aging vs pre-alzheimer
- **normal aging**: slower processing speed, occasional forgetfulness, but no significant impact on daily life.
- **pre-alzheimer's**: memory impairment is more pronounced, especially in forming new memories. There’s also difficulty with complex tasks, executive function, and visuospatial skills. ถ้ามันส่งผลกระทบกับชีวิตประจำวัน คนรอบตัวทัก ก็น่าจะเอะใจได้ละมั้ง?
109
definition of executive function, cognitive function
- **executive function**: Higher-order cognitive processes like planning, decision-making, and multitasking
- **cognitive function**: domains include **memory**, **language**, **attention**, **executive function**, and **visuospatial skills** //impairment in **two or more** of these areas may suggest a condition like **MCI** or a more severe cognitive disorder
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typical symptom of MCI
- MCI - ความสามารถลดกว่าที่ควรจะเป็นในวัยนั้น ๆ แต่ไม่ได้กระทบชีวิตประจำวันขนาดนั้น
- memory problems, misplacing items, language difficulties, attention issues, judgment and reasoning, mood changes
- anteromedial temporal lobe มักเจอใน MCI (while in AD มักเจอที่ temporoparietal association neocortex)
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original diagnostic criteria for mild cognitive impairment (MCI)
proposed by Petersen et al. [in 1999]
1. memory complaint, preferably qualified by an informant คนรอบตัวเป็นคนบอก
2. memory impairment for age ลดกว่าที่วัยนั้น ๆ ควรจะเป็น
3. preserved general cognitive function
4. intact activities of daily living (can still perform everyday activities independentl)
5. not demented (not severe enough to meet the criteria for dementia)
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patient evaluation x rehab goal
- impairment: loss or abnormality of a body fx that can be anatomical, physio or psycho —> to minimize impact of impairment
- disability: inability or restricted ability to perform an
activity —> ambulation w gait aid, independence in ADL
- handicap: limits the social role เสียเปรียบยังไงบ้าง —> social re-integrate
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stroke rehab
> goal หลักคือ minimize impact disability handicap & enhance neuroplasticity
- neurological & functional recovery
- mechanism of neurological recovery
- resolution of edema: พอบริเวณนั้นหายบวม หายอักเสบ → neuron ทำงานต่อได้
- reperfusion of penumbra: ตามนั้น
- resolution of diaschisis: diaschisis means shocked throughout คล้ายนิวรอนช็อค ตกใจ ไรงั้นปะ
- cortical reorganization: **neural plasticity** (neuron ข้าง ๆ มาช่วยทำงาน), take month to yrs, influenced by learning
- goal-directed stroke rehab
- physical: prevent immobilization syndrome ให้ขยับข้อเยอะ ๆ ฝึกกล้ามเนื้อ, bed mobility ท่าฝึกลุกขึ้นนั่ง, ambulation ฝึกยืนฝึกเดิน
- occupational therapy: activity daily living, upper limb activity, hand function, cognitive, perceptual, swallowing
- speech therapy: speech, language
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modern rehab method
- robot-assisted therapy: for regulate neural circuit
- virtual reality: for improve neur plasticity
- music reality: for stimulate cortical activation
- mirror therapy: reduce asymmetrical activation btw hemisphere
- motor imagery training: for remodel of brain neural network จินตนาการสำคัญ!
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definition of dementia and MCI
- definition of dementia: progressive **cognitive/behavioral** impairment result in functional impact on daily life
- dementia & MCI is syndrome = มี underlying cause แตกต่างกัน //MCI อาจดีขึ้นได้โดยไม่ progress เป็น dementia นะ
- dementia: AD, vascular, hippocampal sclerosis, lewy body disease
- MCI: no data, unclassify (degenerative?), vascular, depression
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AD ในบท dementia
- pathologic hallmark: **amyloid plaque** (neuritic plaque) เกิดจาก extracellular aggration of Aβ peptide / neurofibrillary tangle เกิดจาก intracellular aggregation of hyperphosphorylated tau protein
- stage of AD: preclinical → prodromal (MCI) → dementia
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biomarker and disease
- Amyloid plaques (β-amyloid) — Alzheimer’s disease
- Neurofibrillary tangles (3R+4R tau) — Alzheimer’s disease
- Lewy body (⍺-synuclein) — Parkinson disease
- TDP-43 inclusion (TDP-43) — Amyotropic lateral sclerosis
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red flag for non-degen dementia
- rapid unexplain decline in fx: degen → prion disease / test → **neuroimaging**, blood test (ตับไตไทรอยด์)
- younger than expected age at symptom onset: degen → frontotemporal dementia, genetic neurodegen
- prominent fluctuation: non-degen → epileptic, toxic or metabo, psychi / degen → dementia w lewy bodies
- acute or chronic high-risk exposure: non-degen → drug w anticholinergic ADR, wernicke enceph
- hx of high-risk behavior: non-degen → syphilis, HIV
- unexplain finding on neurologic and physical exam: non-degen → normal pressure hydroceph, focal lesion e.g. tumor stroke demyelinate / degen → various non-alzheimer’s dementia
- performance on neurocognitive testing incongruent w clinical history: non-degen → psychi, sensory impair, sleep impair / degen → behavioral variant frontotemporal dementia / test → psychi wuestionnaire
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investigation AD
- CSF: ↓ Aβ42/Aβ40 / ↑ Phosphorylated tau 217
- blood test: ↑ Phosphorylated tau 217
(Aβ42 แย่ท้อกซิก / Aβ40 ดี)
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modify risk factor for dementia
- midlife (45-65yo): hearing loss, traumatic brain injury, HT, alcohol consumption, obesity
- late life (>65yo): smoking, depression, social isolation, physical inactivity, diabetes
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รวมมิตรตัวอักษรสีเหลือง in dementia syndrome
- ไม่เหลืองแต่น่าจำ: ฟีลแบบจจทุกคนมี copathology
- cholinesterase inh (↓metabolism of Ach → enhance postsynaptic stimulate): donepezil → approved for all severity of AD / galantamine → has nicotinic and muscuranic effects / rivastigmine- also inh butyrylcholinesterase
- antipsychotics → ↑risk of stroke and death in individuals w dementia. FDA mandates black box warning
